Autonomic Pharmacology (Ar) - Lec 02 - Adrenergic Receptors

Summary

This educational video script delves into the intricate world of adrenergic receptors, highlighting their crucial roles in the body's sympathetic system. It explains pre-synaptic and post-synaptic receptors, the concept of second messengers, and the unique functions of different adrenergic receptors, such as Alpha 1, Alpha 2, Beta 1, Beta 2, and Beta 3. The script provides insights into how these receptors influence various physiological processes, from muscle contractions to heart rate, and discusses the implications for medical treatments, including the development of selective drugs targeting specific receptor subtypes.

Takeaways

• 🧠 Pre-synaptic and post-synaptic receptors are distinguished by their location relative to the synapse, with pre-synaptic receptors regulating neurotransmitter release from the neuron and post-synaptic receptors receiving the signal on the target cell.
• 🔗 The concept of second messengers is crucial as they are intermediaries that help receptors perform their functions, except for ion channel-linked receptors like the nicotinic acetylcholine receptor, which produce immediate outcomes without them.
• 🌟 Adrenergic receptors are significant, with 70% of all receptors in the body being G protein-linked receptors, including the adrenergic receptors discussed in the script.
• 🔑 Alpha-1 receptors are primarily associated with vasoconstriction in blood vessels, but they can also cause contraction in the uterus and dilation of the pupil, with the exception of causing relaxation in the gastrointestinal tract and urinary bladder due to the presence of a specific potassium channel.
• 🔄 Alpha-2 receptors are predominantly pre-synaptic, regulating the release of norepinephrine and contributing to a calming effect, with over 90% of them located on nerve terminals.
• ❤️ Beta-1 receptors are most notably found in the heart, where they increase cardiac properties, making them potential targets for drugs treating arrhythmias or tachycardia.
• 🏃 Beta-2 receptors are vital for the 'fight or flight' response, increasing blood flow to muscles, facilitating neuromuscular transmission, and causing bronchodilation, among other effects.
• 🏋️ Beta-3 receptors are mainly found in adipose tissue, where they stimulate lipolysis, breaking down fat cells, but their uneven distribution makes them less useful for weight loss therapies.
• 🔄 The activation of beta receptors increases cyclic AMP (cAMP) within cells, which then triggers various cellular responses depending on the specific enzymes and effectors present in different tissues.
• 💊 The development of drugs targeting specific subtypes of receptors, such as Alpha-1D for urinary retention without affecting blood pressure, highlights the importance of receptor specificity in minimizing side effects.
• 📚 Understanding the subtypes and functions of adrenergic receptors is essential for medical professionals to make informed decisions about treatments and potential drug developments.

Q & A

What are the two main concepts introduced at the beginning of the script?

The two main concepts introduced are pre-synaptic and post-synaptic receptors, and the term 'second messenger' in the context of adrenergic receptors.

What is the difference between pre-synaptic and post-synaptic receptors?

Pre-synaptic receptors are located on the neuron or nerve terminal that releases the chemical transmitter, and their function is to regulate the release of transmitters. Post-synaptic receptors are located on the receiving cell or tissue and are responsible for the response to the transmitter.

What is a second messenger in the context of cell signaling?

A second messenger is a molecule that is part of a signaling pathway and is activated by a primary messenger, such as a hormone or neurotransmitter. It often functions within the cell to amplify the signal and trigger a cellular response.

What is unique about the nicotinic acetylcholine receptor compared to other receptors?

The nicotinic acetylcholine receptor is unique because its activation can lead to an immediate outcome without the need for a second messenger. It is an ion channel-linked receptor that, when activated, opens a gate allowing sodium ions to enter, leading to depolarization.

What percentage of receptors in the body are G protein-linked receptors?

Approximately 70 percent of the receptors in the body are G protein-linked receptors.

What are the five common types of adrenergic receptors that adrenaline or noradrenaline can act upon?

The five common types of adrenergic receptors are Alpha One, Alpha Two, Beta One, Beta Two, and Beta Three.

What is the primary function of Alpha One receptors in blood vessels?

The primary function of Alpha One receptors in blood vessels is to cause vasoconstriction, which narrows the blood vessels.

How does the activation of Alpha One receptors lead to vasoconstriction?

Activation of Alpha One receptors leads to the activation of G protein (Gq), which increases inositol trisphosphate (IP3) levels, resulting in increased calcium levels. This increase in calcium causes contraction of the blood vessels.

What is the primary location and function of Alpha Two receptors in the body?

More than 90 percent of Alpha Two receptors are pre-synaptic, primarily located on nerve terminals, where they regulate the release of neurotransmitters, often inhibiting their release.

What are the main functions of Beta Two receptors in the body during physical activity, such as running?

Beta Two receptors are responsible for vasodilation in skeletal muscle blood vessels, facilitation of neuromuscular transmission, increasing potassium stores in muscles, bronchodilation, increasing blood glucose levels, and adjusting intraocular pressure during changes in external air pressure.

Why are Beta 3 receptors not ideal for treating obesity despite their role in lipolysis?

Beta 3 receptors are not ideal for treating obesity because they are not evenly distributed throughout the body. They are more prevalent in the upper half of the body and face, and less so in areas like the belly, which limits their effectiveness in uniformly reducing body fat.

What is the common second messenger activated by all types of beta receptors?

The common second messenger activated by all types of beta receptors is cyclic AMP (cAMP).

How do beta receptors, despite increasing cyclic AMP, result in different cellular responses?

Different cellular responses occur because the increase in cyclic AMP activates different protein kinases and subcellular components depending on the cell type, leading to varied effects despite the common second messenger.

Outlines

00:00

📚 Introduction to Adrenergic Receptors

The script begins by introducing the topic of adrenergic receptors, emphasizing the importance of understanding pre-synaptic versus post-synaptic receptors and the concept of second messengers. It explains that pre-synaptic receptors regulate the release of neurotransmitters from the neuron or nerve terminal, while post-synaptic receptors are found on the receiving cell and are influenced by the neurotransmitter. The script also highlights the unique role of ion channel-linked receptors, such as the nicotinic acetylcholine receptor, which produce immediate outcomes without the need for second messengers.

05:00

🔍 Exploring Adrenergic Receptor Subtypes

This paragraph delves into the different subtypes of adrenergic receptors, including Alpha 1, Alpha 2, Beta 1, Beta 2, and Beta 3. It clarifies that 70% of receptors in the body are G protein-linked receptors, which act through second messengers. The paragraph also discusses the specific functions and locations of Alpha 1 receptors, such as causing vasoconstriction in blood vessels, contraction in the uterus, and dilation of the pupil in the eye. It mentions the subtypes of Alpha 1 receptors and their distinct roles in different tissues.

10:03

🌟 The Role of Alpha 1 Receptors and Second Messengers

The script explains the molecular mechanisms behind the actions of Alpha 1 receptors, focusing on their activation of G protein (Gq), which in turn increases inositol trisphosphate (IP3) and calcium levels. This increase in calcium leads to contraction in various tissues, such as blood vessels, the uterus, and the radial muscles of the eye, resulting in mydriasis. However, in the gastrointestinal and urinary tracts, the presence of a calcium-dependent potassium channel leads to relaxation instead of contraction when Alpha 1 receptors are activated.

15:07

🛡️ Alpha 2 Receptors: Pre-Synaptic Inhibition

This section discusses the role of Alpha 2 receptors, which are predominantly pre-synaptic and function to regulate the release of norepinephrine. By inhibiting the release of neurotransmitters, Alpha 2 receptors have a calming effect on the body. The script suggests that drugs that activate Alpha 2 receptors can be used to treat anxiety and stress by reducing the release of norepinephrine, leading to a more relaxed state.

20:11

🏃‍♂️ Beta 2 Receptors: Enhancing Performance

The script highlights Beta 2 receptors as essential for enhancing physical performance during activities like running. Beta 2 receptors increase blood flow to muscles, facilitate neuromuscular transmission, and promote potassium shift from the blood into muscle cells. They also cause bronchodilation for easier breathing and increase blood glucose levels for energy. Additionally, they are involved in the secretion of aqueous humor in the eyes, which is crucial for maintaining intraocular pressure during activities that increase air pressure on the eyes.

25:11

🤰 Beta 2 Receptors in the Uterus: Protection During Stress

This paragraph explains the protective role of Beta 2 receptors in the uterus during times of stress. Beta 2 receptors cause uterine relaxation, which can prevent the risk of abortion if a pregnant woman experiences fear or stress. The script also touches on the potential side effects of Beta 2 receptor activation, such as tremors due to facilitated neuromuscular transmission, which can be mitigated with beta blockers.

30:15

🔥 Beta 3 Receptors: Fat Melting Controversy

The script addresses the misconception about Beta 3 receptors and their role in fat melting. While Beta 3 receptors do induce lipolysis in adipose tissue, their uneven distribution in the body limits their potential for weight loss. The paragraph clarifies that stimulating Beta 3 receptors would not result in uniform fat loss across the body, which is why there are no Beta 3 agonists among drugs treating obesity.

35:16

🔬 Beta Receptor Function and Cyclic AMP

The final paragraph wraps up the discussion on adrenergic receptors by explaining the common second messenger activated by all Beta receptors, cyclic AMP (cAMP). It clarifies that the different functions of Beta 1, 2, and 3 receptors are due to the specific enzymes and effectors activated by the increased levels of cAMP in their respective cells. The script emphasizes that the ultimate effects of receptor activation are determined by the subcellular components that respond to the second messenger.

Keywords

💡Adrenergic receptors

Adrenergic receptors are a class of cell surface receptors that respond to the stimulation by adrenergic substances such as adrenaline and noradrenaline. They play a crucial role in the body's stress response and are central to the video's theme of understanding the sympathetic nervous system. The script discusses different types of these receptors, including alpha and beta receptors, and their specific functions in the body.

💡Pre-synaptic and post-synaptic receptors

These terms refer to the location of receptors in relation to the synapse, the junction between two nerve cells. Pre-synaptic receptors are located on the neuron that releases neurotransmitters, while post-synaptic receptors are on the receiving neuron. The video script uses these terms to explain how neurotransmitters regulate the transmission of signals between neurons, with examples of alpha 2 and beta2 receptors.

💡Second messenger

A second messenger is a part of a signaling pathway that relays signals from a cell's surface to the inside of the cell, often leading to a change in cellular function. In the context of the video, second messengers like G proteins or kinases are crucial for the function of many receptors, including adrenergic receptors, as they translate the binding of a neurotransmitter to a cellular response.

💡Nicotinic acetylcholine receptor

This is a type of ion channel-linked receptor that responds to the neurotransmitter acetylcholine. The video script highlights this receptor as unique because its activation can lead to an immediate outcome, such as the opening of a gate and influx of sodium ions, without the need for a second messenger. This is in contrast to most other receptors that operate through second messengers.

💡G protein-linked receptors

G protein-linked receptors, also known as G protein-coupled receptors, are a large group of receptors that include adrenergic receptors. They are so named because they use G proteins as second messengers to transduce signals. The script emphasizes that 70 percent of the body's receptors are G protein-linked, acting through second messengers to elicit various physiological responses.

💡Alpha-1 receptors

Alpha-1 receptors are a subtype of adrenergic receptors that, when activated, typically cause vasoconstriction in blood vessels, among other effects. The video script explains that these receptors have been further divided into subtypes, such as alpha-1a, alpha-1b, and alpha-1d, each with specific functions and distributions in the body.

💡Beta-2 receptors

Beta-2 receptors are another subtype of adrenergic receptors that are associated with a variety of beneficial effects during stress or exertion, such as vasodilation in skeletal muscles and bronchodilation. The script describes beta-2 as 'kind' because of its role in facilitating muscle contraction and supporting the body's response to physical stress, like running from danger.

💡Beta-3 receptors

Beta-3 receptors are discussed in the script as being predominantly found in adipose tissue, where they are involved in lipolysis, the breakdown of fat. The video notes that while stimulating these receptors could theoretically aid in weight loss, their uneven distribution in the body limits their practical application for this purpose.

💡Cyclic AMP (cAMP)

Cyclic AMP is a second messenger that plays a key role in many cellular processes. In the context of the video, beta receptors, when activated, increase the levels of cAMP within cells. The script explains that the specific effects of this increase depend on the cellular context, leading to different outcomes in various tissues, such as increased contractility in the heart or relaxation in fat cells.

💡Vasoconstriction

Vasoconstriction refers to the narrowing of blood vessels, which is typically brought about by the activation of certain receptors, such as alpha-1. The video script uses this term to describe the physiological response that occurs in blood vessels when alpha-1 receptors are stimulated, leading to an increase in blood pressure.

Highlights

Introduction to adrenergic receptors and the importance of understanding pre-synaptic and post-synaptic receptors.

Explanation of the concept of second messengers in the context of receptor function.

Distinction between pre-synaptic receptors regulating neurotransmitter release and their unrelatedness to the function of the target tissue.

The unique role of nicotinic acetylcholine receptors as the only type acting without a second messenger for immediate response.

Overview of the four main types of adrenergic receptors and their prevalence, particularly the dominance of G protein-coupled receptors.

Detailed discussion on Alpha 1 receptors, their subtypes, and their effects on various body parts such as blood vessels and the eye.

The role of Alpha 1 receptors in causing vasoconstriction and the underlying mechanism involving G protein and calcium levels.

Exception to the rule: Alpha 1 receptors causing relaxation in the gastrointestinal and urinary tracts due to the presence of a specific potassium channel.

Alpha 2 receptors' predominant location on pre-synaptic terminals and their regulatory function on norepinephrine release.

The therapeutic use of drugs that activate Alpha 2 receptors for calming effects and potential applications in treating anxiety.

Beta 1 receptors' significant impact on cardiac function, including increasing heart rate and contractility.

Beta 2 receptors' multifaceted role in facilitating physical activity, including vasodilation in muscles and bronchodilation.

Beta 2 receptors' contribution to muscle performance by increasing potassium levels within muscle cells and its side effect of hypokalemia.

Beta 3 receptors' specific role in adipose tissue and the scientific understanding of their distribution affecting the potential for weight loss therapies.

The common second messenger, cyclic AMP, utilized by beta receptors and the varying effects due to different cellular responses.

Final concepts on the diversity of adrenergic receptor functions and the complexity of their interactions at the subcellular level.

Transcripts

hello everyone we will specify this video for  illustration of adrenergic receptors before I

start explaining this adrenergic receptors I want  to mention two concepts the first concept I want

you to know is pre-synaptic receptors versus  postsynaptic receptors what does pre-synaptic

and postsynaptic mean because you will hear about  these terms very often while you study number two

we want to discuss a term called second messenger  what the second messenger mean let's start with

the first concept pre-synaptic and postsynaptic  consider this any nerve fiber this is the nerve

body and it's connecting to another nerve body  anywhere either in CNS or prayfully if there is

a receptor present here let's call it Alpha  2 or beta2 and if the same receptor is also

present here Alpha 2 and beta2 remember that  this attachment or the space here is called

synapse which of these are called postsynaptic  and which are pre-synaptic look at the direction

of the chemical transmitter from where it comes  and to where it goes if the chemical transmitter

is moving in this direction from the sill to this  one or let's assume this is a tissue instead and

this is a nerve terminal and signal is moving  in this direction then the receptors present

on the neuron or nerve terminal which releases the  transmitter is called pre-synaptic pre because the

space is called synapse and it's located before so  it's pre-synaptic on the same principle the other

receptors present on the cell or this tissue are  called postsynaptic this is for the terms pre-ampo

synaptic okay now before we dwell into details may  I ask you does this presynaptic receptor has in

anything to do with this tissue or its function  is only about its own nerve cell its function

stops in here so the spray synaptic receptor  present on any nerve terminal or any neuron

releasing transmitters if you say pre-synaptic  then you'll mean that its only function is to

regulate the release of transmitters from this  nerve terminal or this cell releasing transmitters

however it has nothing to do with the tissue  itself or the responder on the other hand if

we say that the transmitter is released from here  to here in this direction this is the receptor is

called pre-synaptic and this one is a postsynaptic  to avoid any confusion if you hear the term

pre-synaptic receptor from now till we finish  all of the lectures when you hear pre-synaptic

then it means these are the receptors located at  presynaptic membrane its function is to regulate

transmitters release so some of them increase  others decrease as we will see now for now if

you hear pre-synaptic then its function is not  in the tissue but it's too regulate transmitter's

release this is the first concept second one is  something called second messenger naturally we

will specify a huge part in general pharmacology  chapter only for receptors we will discuss them

in detail but for now at least you know most  of the receptors are present on cell membrane

if this is a cell then the receptor is here on  cell membrane the receptor doesn't ever perform

any function when it bind to its Agonist it can  only act through something called second messenger

the second messenger might be a g protein it might  be a kinase protein kinase it might be tyrosine

kinase and so on or this receptor might be working  through ION channel in other words there is no

receptor working directly like this except for  focus on this one except for only one type of

receptors its activation can lead to immediate  outcome do you know which one this might be let me

remind you do you remember ganglia from the post  video this ganglia contains acetylcholine when

released it opens a gate do you remember its name  this gets called nicotinic acetylcholine receptor

this receptor here called nicotinic acetylcholine  receptor is the only type of receptors which by

its activation the gate opens resulting in sodium  ion influx leading to depolarization of tissue so

the only type producing immediate outcome  and acts quickly without second messenger

is this type called ION channel linked receptor  if you have any skill question State on this

the only type of receptors that has no second  messenger then it is the first type of receptors

naturally we will explain all of this in detail on  General chapter but for now at least you have an

idea about it so it is the first type called iron  Channel LinkedIn receptor except for this one any

other type of receptors X through second messenger  now how many types of receptors are present

in your body you have four types I won't discuss  them in detail now however you should know that 70

percent offers receptors in your body 70 percent  of the overall number of receptors present inside

your body are something called G protein LinkedIn  receptors so 70 percent of receptors inside your

body are G protein linked receptors like this  one we are explaining in this video which is

adrenergic receptors all of the other energy  receptors are G protein LinkedIn receptors [Music]

don't forget this 70 percent receptors we have  are G protein LinkedIn receptors acting through

second messenger the second messenger might be a  geoprotein protein kinase ION channel or whatever

this is the second concept let's now talk about  the types of adrenergic receptors and discuss

them in detail in the past video physiology  introduction I told you that adrenergic system

or sympathetic System main transmitter is more  adrenaline or nor epinephrine and when it is

released it can affect or activate five types of  receptors first type is Alpha One Second times

Alpha two third is beta1 fourth is beta2 and the  last one is beta 3. those are the five common

types of adrenergic receptors that adrenaline  or noradrenaline can act on and as I told you

any tissue has one type of this as predominant  one it it may indeed have more than one type

but only one is the predominant exert in the most  Market influence let's talk about this Alpha One

firstly discussing its sites functions and its  second messenger which type of second messenger

this Alpha One before anything you should know  that recently there is nothing called Alpha One

anymore it's divided into subtypes we now have  subtype a b d and there are more but only keep

these three in mind Alpha 2 is divided into a  b and c we can no longer say Alpha One and stop

instead we say that a certain tissue has Alpha  One a specifically they are slightly different

from another tissue with Alpha 1D and so on  the first and the most important side for

this Alpha receptor is blood vessels most of  blood vessels you have contain Alpha and its

activation results in vasoconstriction if you want  to be more scientifically exact it is one alpha a

specifically most blood vessels contain Alpha  1 a receptor its function is vasoconstriction

number two is the uterus Alpha receptors in  the uterus also cause contraction however it's

somehow weak in there so I don't want someone  to say that we can make use of this receptor to

induce an abortion in a pregnant woman it does  cause contraction but not so strong that it

could lead to abortion consider this effect to be  theoretical theoretically it can cause contraction

third side is the eye he is the eye this is the  pupil here is something called radial muscles

that you call dilator pure Pele this is a little  pupily contain Alpha One when it is activated it

leads to contraction note that alpha 1 is always  causing contraction or constriction and you will

see the reason when this Alpha is activated in  the eye it leads to contraction of the radial

muscles of the eye so the pupil dilates and when  the pupil dilates it's called mydriasis as you

know from physiology when someone experiences  sympathetic stimulation his people must dilate

for a better Vision in order to face the danger  fourth site for all sound receptors this is git

and this is a urinary tract let's talk about them  as one in both of them we always have a hole and

we always have a sphincter Alpha One if it's  found in the wall then it causes relaxation and

this is an exception because I told you although  causes contraction if it's found in the wall of

the urinary system it also causes relaxation  but in sphincters it causes contraction if you

want to be more scientifically exact here in  this sphincter we have Alpha One a and Alpha

1D so in this sphincter we have Alpha One a and  the cause and contraction why are we saying this

that's because when we discuss the drugs I'll  tell you that whenever you invent a drug it's

better to Target only one specific subtype why  because if you want to act on blood vessels only

then you should Target Alpha 1A if you want to  act on sphincter you have Alpha One A and E then

you should choose a drug that acts on Alpha 1D  considering that this subtype is not very common

except in sphincters so if you have a patient  complaining of hearing retention which one is

accused of course it is the alpha receptor  so we should give him Alpha blocker when we

block this Alpha receptor the sphincter opens  and urine come out and the post we used to do

this not very far in the past but about 20  years ago when someone complained of hearing

retention we used to give him Alpha blocker  do you know what did these people complain

of these patients who received alpha blockers  complain firstly of dizziness do you know why

was he dizzy it's simple as you can see when I  give him Alpha blocker to block Alpha here which

was responsible for sphincter contract action  and urine retention this Alpha blocker I gave

it to the patient was non-selective so it looked  Alpha here and it did solve this problem however

it also blocked Alpha receptors and blood vessels  leading to loss of vasoconstriction resulting in

low blood pressure so if you are smart enough  and you want to invent a drug that only acts on

the sphincter without affecting blood pressure  the new inventor drug that blocks only Alpha 1D

why this Alpha 1D we cause its present only in  sphincters blood vessels doesn't have Alpha 1D

this is the progress in medicine and these are  the new drugs but don't mind with their names now

I only want to show you how important subtype  functions can be a new subtype discovery means

that a new drug is on the way which is more  selective this High selectivity decreases its

side effects on other tissue these are most  of the parts in your body that contain Alpha

receptors there is only one place left which  we don't care about that much but let's have

a quick Glimpse on it anyway do you remember in  the past video when I told you about sweat glands

do you remember the autonomic supply of sweet  glands is it sympathetic or parasympathetic yes

they are supplied by sympathetic system but when I  told you although they are supplied by sympathetic

their transmitter is acetylcholine that's why  we called the nerves applying these sweat glands

sympathetic cholinergic so The receptors in this  glands should respond to acetylcholine accordingly

they are not supposed to belong to this family  of adrenergic receptors however some of the sweat

glands especially those in the palms and forehead  still obey the rule in other words they are

supplied by sympathetic and their nerve endings  released nor adrenaline and the responders that

respond to it and make your hand and foreign so  we have two types of sweet glands in our body one

that's cholinergic and this is the most common all  over the body and one that's adrenergic present in

the forehead and the Palms because its nerve is  sympathetic release another adrenaline which acts

on Alpha One again if we want to enumerate the  size of Alpha One receptors they are present in

blood vessels causing vasoconstriction they are  present in the uterus their effect is weak but

still contraction they are present and the radial  muscles of the IV cause contraction but be aware

of this for McQ they don't cause contraction  of the pupil they indeed cause contraction but

not for the pupil they cause contraction of the  radial muscles of the eye they are also present

in the role of git and urinary tract causing  relaxation they are present in the sphincters

causing contraction we are missing only one thing  which you may be wondering about now [Music]

in all of these places why do alpha 1 receptors  cause contraction everywhere except in the role

of git and urinary tract where they cause  relaxation here we need to return to the

concept of second messenger that I told you about  at the start of the video this is explained by

second messenger regarding Alpha One if this is  a sill and this is Alpha 1 receptor present on

cell membrane when it's activated it activates  something called G protein queue time we have

three types of G protein and maybe there are more  than just three as you know from biochemistry we

have three types of G protein g stimulatory g  inhibitory and third type is called GQ is short

for query or questionable when this GQ works it  increases something called inocetyl triphosphate

or ip3 and when ip3 increase it increases calcium  you know from physiology that this calcium is an

incinerator calcium never acts for the sake of  common good it's never possible for calcium to

increase causing relaxation increased calcium  level in any cell if that cell was contractile

it leads to contraction this is why blood  vessels contract you know that when alpha

one works it leads to vasoconstriction this is  explained on the molecular level by these steps

Alpha One activation turns on GQ increase in ip3  level which increases calcium level this increased

calcium and the reason behind vasoconstriction  okay so much so that when we want to induce

relaxation in any tissue we use drugs I'll tell  you about later they are called calcium channel

blockers calcium blockers because you know that  the calcium always leads to contraction but then

what drives gltm urinal bladder to deviate from  this rule it's suppose that the alpha activates GQ

increase in ip3 includes in calcium do you know  why Joy can urinal Builder rules deviate from

the rule it's very simple reason if we assume  this to be a sill from git wall when calcium

level is increased within the cell of git wall it  opens a certain type of potassium Channel called

calcium dependent potassium Channel originally  increased calcium level leads to activation

of a certain enzyme called don't bother with  the name but anyway it's called myosin light

chain kinase this myosin like chinkinis  is the one causing contraction however

in the whole of the git and urinary tract  this enzyme is absent instead there is a

certain potassium Channel when calcium level  is increased it opens this type of potassium

Channel and you know what when potassium  channels open this cell is somehow paralyzed

this cell now is paralyzed and this paralysis  in medical terms is called relaxation again

if some examiner wants to intimidate you you're  an oral exam like this dear student can you tell

me why doesn't this Alpha have any good intentions  tell him indeed it doesn't because it always cause

contraction he will then ask you but why tell  him because it turns on GQ and GQ increased

ip3 leading to increased level of calcium if he  wants to pressurize you further he would then ask

you and what does calcium do tell him it acts  on enzyme called myosin lyching kinase causing

contraction he would then say but I think it can  cause relaxation git and urinary bladder rules

tell him that this is right because the rules  doesn't have this enzyme instead they have a

potassium Channel called calcium dependent  potassium channel that opens in response to

increased calcium leading to hyperpolarization of  the wall resulting in relaxation for now this is

all what we need to know about this Alpha so let's  start discussing alpha 2. alpha 2 is too kind

that it won't take too much time I'll only tell  you one word and leave you to your own devices

if I tell you that most of Alpha 2 in your body  more than 90 percent of this Alpha 2 distributed

in your body or pre-synaptic that's it I'm saying  no more I'm leaving you to your own devices what

does pre-synaptic mean it means it's present on  the nerve terminal if this is a nerve terminal and

this is a tissue and this is synapse does alpha 2  act on tissue or on its nerve terminal of course

on the nerve terminal its function is regulatory  as I told you before and this Alpha 2 is nearly

always opposite of alpha one this one was far  from good always contraction and so on on the

other hand this one is inhibitory it decreased  lower epinephrine release calming you down

patience relax humans relax who in the nervous  one he is the one with malfunctioning Alpha 2

and since Alpha 2 is malfunctioning then this  one is releasing more than enough norepinephrine

such conditions when someone complains of always  feeling nervous and you want to calm him down give

him a drug that activates Alpha too we invented  drugs for this purpose to activate this Alpha

too for example if a drug addict came to us  now he has repented open the cigarette booth

and he is no longer taking drugs he may come  to you complaining of an anxiety and tension

in this situation if you want to calm him down  you tell him that instead of taking substance

for relaxation stop this and I'll give you  a drug that stimulates Alpha 2 receptors

when I stimulate your Alpha 2 and the brain and  peripheral nerves it's a pre-synaptic receptor

that decreases nor epinephrine release so you will  be calmer and more relaxed this is the best use

of these drugs that activates Alpha 2 and we call  them selective Alpha two agonists or stimulants we

have Alpha 2 and many other tissue it's also  present postsynaptic but it's somehow weak

I told you that more than 90 percent of them are  pre-synaptic for regulator nor epinephrine release

decrease in norepinephrine release okay now let's  shift to betalon beta1 is the commander of the

heart so that it's called cardiac beta1 its most  well-known place is the heart and its activation

leads to increase all of the cardiac properties  count with me from heart rate to automaticity

rhythmicity contractility and so on it increases  all of the cardiac properties and when you have a

patient complaining of arrhythmia or tachycardia  this bet alone could be responsible for this

then you have to give him a beta blocker until now  we don't know if it has subtypes or not let's hope

to discover its subtype soon I'm sure it has  subtitles but this is not important for you so

Peter 1 is present in the heart not only there  but it is also present in the kid D if you want

to Target this beta 1 in the heart search for  its subtypes and invent a drug targeting them

in order to be more selective those are the most  well-known places for beta1 it's present in the

kidneys and it's present in the heart this beta  one is also present in liposites or adipocytes fat

tissue cells however beta 3 is the predominant  type there so if someone asks you whether your

adipose tissue have bitter one then the answer  is yes but when we talk about adipocytes or fat

cells it's always the beta 3 that has the most  of the effect there it is their specialty the

playground of beta 3 is adipocytes if betalon is  mentioned just don't forget it's present in the

heart and in the kidney this is all what I want  you to know now beta2 beta2 is called the kind

beta2 why the kind by the way receptor is taken  number two are always kind and considerate and

receptors taken number one are almost always Rogue  now why are beta 2 called the coin beta2 because

it's the one responsible for running this is the  hero 7u when God forbid a dog chases you or while

you are climbing the stairs perish the thought a  habit cat runs into you in the dark this beta 2

is the one saving you on such occasions in Egypt  when we Face something terrify we say that Ronin

is half of their carriage and this beta2 is the  one responsible for this carriage's half but why

number one if I am facing a threat and I need  to run away what is the first thing I need it

is skeletal muscles correct I need skeletal  muscle cells so this beta2 dilates your blood

vessels present in skeletal muscles to give them  more blood so you can run do you know why it's

because if beta 2 didn't do this Alpha One would  cause vasoconstriction and this is very bad if you

try to run you would have a cram however this  beta2 prevent this one from affecting skeletal

muscles skeletal muscles blood vessels are dilated  under the effect of beta 1 not only this but do

you remember when I told you that skeletal  muscles have nerve endings releasing a style

cooling do you remember the name of the receptor  respondent for acetylcholine from the post video

it's a gate called nicotinic acylcholine receptor  muscular type do you remember this word this one

is supposed to be acetylcholine then what is  the rule of beta2 beta 2 makes this receptor

cool nicotine cell cooling receptor become more  sensitive to acetylcholine why we need it to be

more sensitive so we can run quickly so we can  depend on our muscles this is the term that you

read and wonder about its meaning this is called  facilitation of the neuromuscular transmission

this term means that beta2 increases blood flow  to the muscles and also makes this receptor that

respond to a style cooling become more sensitive  resulting in a quicker and better response these

are two functions within the muscles still we have  a third one but before the third one let me remind

you with something you had in physiology in order  for a cell to have action potential one sodium ion

gets inside for exchange of one potassium ion you  call this action potential and depolarization now

in order for muscle to contract cause a muscular  contraction shouldn't sodium get inside cells

potassium get out and this process occur very  rapidly so we can run but if you don't have

potassium in your muscles can you run if potassium  stores in muscles are low can you start running

sodium get inside muscle cells cause  interpolarization but it wouldn't find

potassium to get out for exit change this can  result in disruption of the action potential and

this is the rule of beta2 receptors these beta2  receptors Drive potassium ions from blood into the

cells causing something known as potassium shift  it quickly draws potassium ions from the blood

and push them inside muscle cells so they have  sufficient potassium stores for Action potentials

facilitate muscle contraction muscle contracts  quicker without fatigue they increased potassium

levels in cells but they decreased its level in  the blood resulting in hypokalemia potassium is

not sufficient in the blood be careful not to  mix these effects with each other I want you to

understand when I tell you how does beta 2 affect  potassium if you say it causes hypokalemia you're

right although it didn't mean to cause hypokalemia  beta 2 didn't intend to cause hypokalemia

specifically it only intends to increase potassium  ions inside the muscles so it draws them from

Blood In other words beta 2 had good intentions  it only wanted to facilitate muscle contraction

but it didn't intend to cause hypokalemia these  are three effects on the level of muscles it

increases blood flow it facilitates neuromuscular  transmission and it draws potassium from blood

into the muscles causing hypokalemia not only this  but you know that when we are running we need our

heart right heart rate is increased and this  beta 1 supposed to increase contractility this

beta2 helps beta 1 through coronary dilocation  dilation of the coronary artery so its causing

dilatation in two places skeletal muscle blood  vessels and coronary arteries both of them you

need during running these two places has nothing  to do with Alpha for now during running skeletal

muscles and Corners are under beta 2 controlled  which causes vasodilation we didn't finish it

while you are running you need to paint so what  do you think happened to broncoi do you think

they constrict you will die then beta 2 causes  bronchodilatation so you can breathe easily

during running [Music] and when you run don't you  need high blood sugar so you can think a muscle

can contract where can you give the sugar from  from the liver liver is stored in sugar in the

form called glycogen okay this beta2 dissolves  some of this July cushion releasing glucose into

blood to enhance muscle performance and cognition  function so you can react you can decide how to

escape from this dog which root is the best  sugar helps you in this count with me all

of these functions I don't memorize them so let's  try to remember them together it has three effects

on muscles it causes vasodilation of skeletal  muscles blood vessels and it cause facilitation

of neuromuscular transmission resulting bitter  muscular performance and it increased potassium

stores inside muscles from where does it come  from blood number four it increases blood

glucose level from where from liver hell or is  analysis number five it cause bronchodilatation

so you can take good breaths while you're  out number six while you run air pressure

can affect the eye if you are running quickly  air pressure is increased on the eyes [Music]

let's assume this is an eye this is cornea  and this is scalero this is front image

this is the iris this is a lens this is suspensory  ligament of the lens this is a ciliary body

anchoroid here is something called ciliary  epithelium this ciliary epithelium which has

beta-2 receptor it's responsible for secretion  of the fluid inside your eye which preserves

intraocular attention URI contain fluid in  the interior and posterior Chambers both of

them are filled with fluid cooled aqueous humor  where does it come from from epithelium line and

ciliary body called ciliary epithelium it has  beta-2 responsible for secretion of this fluid

what does this have to do with running while you  run air pressure on the ice is increased and we

cannot live discontinue here are pressure sensors  they sense the pressure once they feel increased

air pressure they activate B tattoo receptor  to increase equals human secretion it doesn't

intend to harm you with increasing equals humor  but to confront this increase in the air pressure

during running now you stop and air pressure is  back to normal then this equals humor is absorbed

and drained through something called angle of the  eye to Canal of Islam to the episcular veins and

lymphatics that's okay all of this and we didn't  deviate from the word running running is half of

the carriage this beta 2 is the hero responsible  for this Carriage okay is there anything else yes

there is something else imagine if you have a  pregnant woman in your clinic who was unable

to conceive for many years 15 years or so then she  finally was able to get pregnant now she's praying

for God every day and doing charity because she's  now pregnant imagine if this brilliant woman is

being chased by a stray dog what a nurse at this  if she was frightened and ran away she would

likely have an abortion that's why God's blessing  her with B tattoo receptors in the uterus do you

remember when I told you that uterusalem but it's  effects on remarkable on the other hand the tattoo

effect on the uterus is Extreme really powerful  it causes you to rain relaxation during danger

to avoid abortion do you get it now why we are  calling this kind B tattoo receptor so be careful

during exams as some examiner may try to deceive  you and ask you do you know a drug that can block

beta-2 receptor tell him I can understand if  you want a drug block on all types of receptors

together but why Peter 2 specifically it didn't  do anything bad maybe the only answerable effect

of it is when it improves muscle contraction by  facilitation of the neuromuscular Transmission in

order to improve performance it might sometimes  cause handshake this facilitation can sometimes

result in this Chic which we call tremors this  may be the only undesirable effect of beta2

sometimes people can complain to you of hand  shaking especially those working in a shooting

range these people may complain of shaky hands  during targeting tell him it's because of beta

2 in your hands it's slightly overactive in  your hands during their facilitation of the

neuromuscular transmission and this is what causes  these Tremors this is the only answerable effect

and I can prescribe a beta blocker in this  situation to remove these trimmers if this

man wants to cheat he may have a shooting test  and he wants a steady hands during this test give

him a bit of looker blocking beta receptors  which causes this Tremor so his hand Can Be

steady and he can pass so all in all beta 2 is  always kind and doesn't mean to cause any harm

except for these trimmers this is a very  simple effect now we only have beta 3 left

and you already know something about it by the  way this beta 3 could be considered a different

type of beta 2 is scientifically considered  as a subtitle of beta2 however it's present

in the Edibles tissue causing lipolysis melting  the fat needless to say once you hear that it

melts the fat people who are watching this video  right now will say that's it we have found it you

are thinking about weight loss aren't you this is  good you have a sound mind and you are trying to

make good application of signs however allow me to  destroy your happiness why because if beta 3 had

been uniformly distributed all over your fat if it  had been present in the fat of my face hence all

of my body evenly I would have invented a drug  stimulating it causing lipolysis allowing us to

get rid of this fat without much effort but sadly  enough this beta 3 receptors are present more in

the upper half of the body they are present more  in the face hands but they are not present in

the belly fat accordingly if you stimulate beta3  receptors certain area of your body lose fat but

other areas don't your face would be thinner but  your belly fat will dream in the sea that's why

we couldn't make much benefit from them so if you  see a question in exam asking why don't we have

beta 3 agonists as this receptor are supposed  to induce lipolysis so why don't we have a beta

3 against among drugs treating obesity pick this  peculiar sentence from the choices because it is

not evenly distributed throughout the body this  is the answer there is only one last concept

before we end this video I told you that Alpha  One Second messenger is which type of messenger

I told you that Alpha on Activision turns on a  protein called GQ do you remember all types of

beta receptors when they are activated they turn  on the same second messenger called cyclic amb

when cyclic amp is increased inside sales it  causes all of these effects which we discussed so

why don't they all have the same function why are  beta 1 2 and 3 though in different functions it's

because when cyclic amb is increased it activates  other subcellular components other Kinesis kinase

here is different from the one here and here again  so you don't miss this concept if someone asks you

what type are beta receptors present in your body  tell him G protein LinkedIn receptors but how does

this beta receptor function tell him it increases  cyclic amp inside cells but then why beton

receptors in the heart increase contractility  while betatuku's relaxation although both of

them increase their theme cyclic MP tell him it is  not all about cyclic amb but what's present behind

this cyclic amb when cyclic amp is increased and  the harder it activates a certain protein kinase

which is a different from the kinase present in  the cells that are under the effect of bit data 3

so it's not all about the receptor it's not all  about G protein however it's all about further

enzymes final effectors at the subcerial level  remember this so no one can trap you during oral

exams now we have finished the main Concepts about  adrenergic receptors see you in the next video