G-Protein & G-Protein-Coupled Receptors (GPCR) | Cell Surface Receptor | Physiology | Endocrinology

Summary

In this educational video, the host delves into the fascinating world of endocrinology, focusing on cell signal transduction and the pivotal role of G-proteins. The discussion highlights the differences between lipid-soluble and water-soluble hormones, explaining how the latter must interact with cell surface receptors due to their inability to penetrate the lipid cell membrane. The video simplifies complex concepts like G-protein activation, the role of GTP and GDP, and the impact on second messenger systems. It also touches on the physiological significance of these processes, using examples like the sympathetic and parasympathetic nervous systems to illustrate the practical applications of G-protein coupled receptors in medicine.

Takeaways

• 🧬 **Proteins in Cell Signaling**: Almost all active particles in the body are proteins, including channels, pumps, carriers, enzymes, and receptors.
• 🌟 **Hormone Classification**: Hormones can be proteins (water-soluble) or fats (lipid-soluble), which affects their mechanism of action and speed.
• 🚪 **Lipid-Soluble Hormones**: These hormones are slower in action because they must diffuse through the lipid cell membrane to reach intracellular receptors.
• 🔗 **Water-Soluble Hormones**: These hormones bind to cell surface receptors and act quickly, flipping a switch to activate cellular responses.
• 🔑 **Role of G Proteins**: G proteins act as middlemen, linking cell surface receptors to intracellular enzymes, especially for water-soluble hormones.
• 🔄 **G Protein Activation**: G proteins switch from GDP to GTP binding upon activation, which triggers a series of cellular responses.
• 🌡️ **G Protein-Coupled Receptors (GPCRs)**: These are the largest family of cell surface receptors and are crucial for signal transduction of water-soluble hormones.
• 🔋 **Second Messenger Systems**: Activated by G proteins, these systems amplify signals and initiate various cellular responses, such as changes in ion channel activity.
• 🛑 **Termination of Signaling**: GTPase activity converts GTP back to GDP, inactivating G proteins and ending the signal transduction process.
• 🧩 **Integration of Signals**: G proteins integrate signals from cell surface receptors to initiate a cascade of events within the cell, leading to physiological responses.

Q & A

What is the primary reason proteins are involved in most active cellular processes?

Proteins are involved in most active cellular processes because they are capable of being switched on or off, rotating, or undergoing conformational changes, which are essential for their function. This is due to their complex structures, including primary, secondary, and tertiary structures, and post-translational modifications.

How do lipid-soluble hormones differ from water-soluble hormones in terms of their action speed?

Lipid-soluble hormones are slower in action compared to water-soluble hormones because they need to diffuse through the lipid cell membrane, which is a slow process. In contrast, water-soluble hormones can quickly bind to cell surface receptors and initiate a response without needing to pass through the membrane.

Why are cell surface receptors for water-soluble hormones located outside the cell?

Cell surface receptors for water-soluble hormones are located outside the cell because these hormones cannot diffuse through the lipid bilayer membrane. The receptors must be on the outside to bind with the water-soluble hormones directly.

What is the role of the G protein in cell signal transduction?

The G protein acts as a middleman in cell signal transduction for water-soluble hormones. It links the receptor on the outside of the cell with the enzyme on the inside, facilitating the signal transmission across the cell membrane.

What are the three types of G-protein-coupled receptors mentioned in the script?

The three types of G-protein-coupled receptors mentioned are: 1) G-protein-coupled receptors, 2) Ligand-gated ion channels, and 3) Enzyme-linked receptors.

How does the G protein switch from an inactive to an active state?

The G protein switches from an inactive to an active state when a water-soluble hormone binds to the receptor. This binding causes a conformational change in the receptor, which then activates the G protein. The G protein then exchanges GDP for GTP, activating the alpha subunit and leading to the dissociation of the beta and gamma subunits.

What is the function of the GTPase enzyme in the context of G protein activity?

The GTPase enzyme is responsible for breaking down GTP into GDP, which converts the active G protein back into an inactive state. This hydrolysis reaction terminates the activity of the G protein and stops the signal transduction process.

How does the activation of Gq, Gs, or Gi lead to different cellular responses?

The activation of Gq typically leads to an increase in intracellular calcium levels and contraction of smooth muscles. Gs activation increases cyclic AMP levels, leading to relaxation of smooth muscles and increased cardiac contractility. Gi activation inhibits adenylate cyclase, resulting in decreased cyclic AMP levels and a variety of inhibitory effects on the cell.

What is the significance of the seven transmembrane helices in G-protein-coupled receptors?

The seven transmembrane helices in G-protein-coupled receptors provide a complex three-dimensional structure that allows the receptor to span the entire thickness of the cell membrane. This structure is crucial for the receptor's ability to bind the ligand on the outside and interact with the G protein on the inside.

How do different G-protein couplings result in different physiological effects?

Different G-protein couplings result in different physiological effects because they activate different second messenger systems. For example, Gq activation leads to increased calcium levels and muscle contraction, while Gs activation leads to increased cyclic AMP and muscle relaxation. Gi activation typically inhibits these processes, leading to reduced cellular activity.

Outlines

00:00

🔬 Introduction to Cell Signal Transduction and G Proteins

The video begins with an introduction to the topic of cell signal transduction, focusing on cell surface receptors and the role of G proteins. The speaker emphasizes the importance of proteins in biological processes, explaining that almost all active particles in the body are proteins. Hormones, which can be proteins or fats, determine the speed of action based on their solubility. The video sets the stage for a deeper dive into how water-soluble hormones interact with cell surface receptors and G proteins, which are integral membrane proteins that facilitate the signal transmission across the lipid bilayer.

05:02

🧬 The Role of G Proteins in Signal Transduction

This section delves into the specifics of G proteins, which are guanine nucleotide-binding proteins that can bind to GTP or GDP. The speaker explains the mechanism by which water-soluble hormones interact with cell surface receptors, leading to the activation of G proteins and subsequent activation of second messenger systems. The video outlines the three types of G-protein-coupled receptors, which are the most significant family of cell surface receptors, and discusses how these receptors, with their seven transmembrane helices, interact with G proteins and effector molecules to initiate cellular responses.

10:04

🌀 The Activation and Termination of G Protein Signaling

The paragraph explains the trimeric structure of G proteins, consisting of alpha, beta, and gamma subunits, and how they transition from an inactive GDP-bound state to an active GTP-bound state upon hormone binding. The video describes the activation process where the alpha subunit, once active, dissociates from the beta and gamma subunits, leading to the activation of effector molecules like Gq, Gs, or Gi. It also covers the termination of the G protein activity by GTPase, which hydrolyzes GTP back into GDP, thus returning the G protein to its inactive state.

15:06

🚦 The Impact of G Protein Coupling on Cellular Responses

This segment discusses the different outcomes of G protein coupling on cellular responses, depending on whether the G protein is Gq, Gs, or Gi. It explains how Gq activation leads to increases in calcium levels and contraction of smooth muscles, while Gs activation results in the production of cyclic AMP, leading to relaxation of smooth muscles. Gi, on the other hand, inhibits the production of cyclic AMP. The video uses examples from the sympathetic and parasympathetic nervous systems to illustrate these concepts, showing how the same neurotransmitter can have opposite effects on different tissues depending on the receptor and G protein involved.

20:06

💊 Practical Applications and Summary of G Protein Signaling

The final paragraph ties the theoretical concepts back to practical medical applications, discussing how understanding G protein signaling is crucial for comprehending the actions of various hormones and neurotransmitters. It provides examples of how different receptors and G protein couplings are associated with specific physiological responses, such as the vasoconstriction effects of angiotensin II and the dual action of ADH on blood vessels and kidneys. The speaker also promotes their premium courses on endocrine pharmacology and renal physiology, offering a discount code for viewers.

Keywords

💡Endocrinology

Endocrinology is the branch of biology and medicine that deals with the endocrine system, hormones, and their specific receptors on target cells. In the context of the video, endocrinology is the main theme, focusing on how hormones, which are often proteins or lipids, interact with the body to regulate various functions. The video discusses how hormones can be water-soluble or lipid-soluble, affecting how they interact with cell receptors.

💡Cell Signal Transduction

Cell signal transduction refers to the process by which a cell converts one kind of signal or stimulus into another, usually leading to a cellular response. The video emphasizes the importance of signal transduction in endocrinology, particularly how hormones trigger a cascade of events within cells, often beginning with the interaction of the hormone with a cell surface receptor.

💡G Protein

G proteins are a family of proteins involved in signal transduction, coupling the activation of receptors to the activation of other proteins like enzymes. The video focuses on G proteins' role in linking cell surface receptors to intracellular enzymes, especially in the context of water-soluble hormones, which cannot pass through the lipid cell membrane.

💡Water-Soluble Hormones

Water-soluble hormones are hormones that can dissolve in water, making them unable to cross the lipid cell membrane. In the video, the distinction between water-soluble and lipid-soluble hormones is highlighted, with water-soluble hormones requiring cell surface receptors and G protein coupling to exert their effects.

💡Ligand-Receptor Complex

A ligand-receptor complex is formed when a hormone (ligand) binds to its specific receptor on the cell surface. The video explains that this complex is crucial for initiating the signal transduction process, particularly with G protein-coupled receptors, which are activated by water-soluble hormones.

💡Second Messenger Systems

Second messenger systems are intracellular signaling molecules that relay and amplify signals initiated by hormones binding to cell surface receptors. The video discusses how G proteins activate second messenger systems, such as cyclic AMP or calcium, which then initiate further cellular responses.

💡GTPase

GTPase refers to the enzyme activity that hydrolyzes guanosine triphosphate (GTP) to guanosine diphosphate (GDP). In the video, GTPase activity is highlighted as a mechanism to terminate the activity of G proteins, thus ending the signal transduction process once the hormone's message has been delivered.

💡G Protein-Coupled Receptors (GPCRs)

GPCRs are a large group of cell surface receptors that, when activated by a hormone, interact with G proteins to initiate a cellular response. The video emphasizes GPCRs as the primary focus for water-soluble hormones, which cannot directly enter the cell and must rely on these receptors for signal transduction.

💡Catecholamines

Catecholamines are a class of monoamine neurotransmitters that include epinephrine, norepinephrine, and dopamine. The video mentions catecholamines as examples of water-soluble hormones that act through GPCRs, illustrating the diversity of hormones that utilize this signaling pathway.

💡Pituitary Hormones

Pituitary hormones are hormones produced by the pituitary gland, which regulates various physiological functions. The video discusses how some pituitary hormones, despite being produced by glands that typically secrete lipid-soluble hormones, are themselves water-soluble and thus act through GPCRs.

Highlights

Introduction to the topic of cell signal transduction, focusing on cell surface receptors and the role of G proteins.

Emphasis on the importance of proteins in biological systems, including their role in cell signal transduction.

Explanation of how hormones can be proteins or fats, and their solubility affects their mechanism of action.

Detail on the slow action of lipid-soluble hormones due to their need to diffuse through the lipid cell membrane.

Contrast between the fast action of water-soluble hormones that bind to cell surface receptors.

The necessity for water-soluble hormones to have cell surface receptors due to their inability to pass through the lipid membrane.

Description of G proteins as integral proteins that span the entire cell membrane and their role in signal transduction.

Differentiation between lipid-soluble and water-soluble hormones and their respective receptors.

Explanation of the G protein's function as a middleman linking cell surface receptors to intracellular enzymes.

Enumeration of water-soluble hormones, including pituitary hormones, pancreatic hormones, and catecholamines.

Discussion on the structural components of G proteins and their activation mechanism involving GTP and GDP.

The role of GTPase enzyme in terminating the activity of the G protein by converting GTP back into GDP.

Differentiation between the functions of Gq, Gs, and Gi proteins in cellular responses.

The impact of G protein activation on second messenger systems and the generation of cyclic AMP.

Clinical relevance of understanding G protein-coupled receptors in medicine and pharmacology.

Practical examples of how G protein activation leads to physiological responses, such as smooth muscle contraction and relaxation.

Summary of the video's key points and a call to action for viewers to continue their education on the topic.

Transcripts

what's up lovely people this is

mitochosis perfectionist where medicine

makes perfect sense let's resume our

endocrinology playlist we are in the

topic of cell signal transduction today

we'll focus on a cell surface receptor

and the story of the g protein so let's

get started this is my endocrinology

playlist watch these videos in order

especially the last two if you don't

understand this one here's a very

important fact to keep in your mind

almost all of the active particles in

your body are proteins all channels are

proteins all pumps are proteins all

carriers are proteins all enzymes are

proteins or receptors are proteins

anything that's going to be switched on

switched off rotate have a

conformational change anything of this

sort is going to be a protein for a very

simple reason go back to biochemistry

and molecular biology and remember the

story of dna synthesis transcription and

translation and then you have

post-translational modification remember

the primary structure of protein

secondary structure tertiary structures

proteins are complex indeed however

hormones beg to differ they could be

proteins or fat if they are proteins

they are water soluble if they are fat

of course they are water insoluble but

lipid soluble i don't just mean proteins

i mean proteins peptides polypeptides

amy and the entire family as we have

said gazillion times before there is a

ceo followed by a general manager and

then you have employees and independent

contractors only three glands listen to

the pituitary these three glands who

listen to the pituitary produce

steroidal hormones that are fat soluble

and that's why they are slower in action

contrast that with the independent

contractors they produce peptides

proteins and therefore they are faster

why are lipid soluble hormones slow in

action because you have to leave the

plasma protein and then go until you

reach the cell membrane the cell

membrane is lipid and the hormone is

lipid lipid can diffuse through lipid

but this process is very slow i have to

diffuse throughout the cell membrane and

then go through the cytoplasm and then

reach the receptor maybe in the

cytoplasm or the nucleus this is a very

slow process and wait there is more i

then have to tap on the dna knock on the

door hey dna would you like to like

replicate and transcription translation

make me some brand new proteins oh yeah

sure all of this takes time conversely

if your water soluble hormone you just

cannot pass through the membrane because

the membrane is lipid and you are water

soluble therefore you have to stay

outside and then latch onto a cell

surface receptor and this is like

flipping a switch on and just like your

bedroom when you turn on the lights you

just click on the switch and boom the

light is on it's a very fast process

if the hormone is lipid soluble we put

the receptor inside because you can

diffuse through the membrane but if the

hormone is water soluble we have to put

the receptor outside a soil surface

receptor because the hormone cannot

enter through the lipid bilayer membrane

these receptors especially those coupled

to a g protein are integral proteins

because they take the whole thickness of

the membrane if you wanna remember the

difference between integral proteins and

peripheral proteins go back to my

physiology playlist and check the video

titled the functions of protein in the

cell membrane the distinction between

lipid soluble hormones and water-soluble

hormones was discussed before just

remember today's topic is the g protein

we are talking about water soluble

because the receptor has to be on the

outside who's gonna link the receptor on

the outside with the enzyme on the

inside that's the purpose of the

g-protein what are these water-soluble

hormones there are many including the

pituitary hormones pancreatic hormones

parathyroid hormones and your

catecholamines which include epinephrine

norepinephrine and dopamine if you are a

lipid-soluble hormone which is not

today's topic you just diffuse through

the cell membrane which is made of lipid

until you reach your receptor which is

usually in the cytoplasm or the nucleus

then we have a ligand receptor complex

which will activate hormone response

elements which will activate dna first

replication when you convert dna to dna

or transcription which is dna to rna or

translation from rna to proteins all of

this takes a very long time these are

slow acting examples of these fat

soluble hormones you have all of the

steroidal hormones these include the

hormones secreted by your adrenal cortex

zona glomerulosa zona fasciculata zona

reticularis and then add the testicles

testosterone ovaries estrogens and

progesterone moreover there are the

thyroid hormones t3 and t4 as well as

vitamin d all of these are lipid soluble

that's not today's topic today's topic

is the water soluble hormones can you

diffuse to the membrane that's made of

lipid nope i cannot so therefore you

have to put the receptor on the outside

all right the receptors on the outside

the enzyme the actual action is on the

inside who is the middle man that's

gonna connect the receptor on the

outside with the enzyme on the inside

this is the story of the g protein it's

the middle main why do you call it g

protein why not f as in fme because this

is the guanine nucleotide binding

proteins it can bind to gtp or gdp

that's why we call the g protein so here

is your lovely water soluble hormone

it's going to act on a cell surface

receptor of course all receptors are

proteins when this happens you got the

ligand receptor complex which is active

this will activate the g protein the g

protein will then activate the enzymes

known as second messenger systems who's

the first messenger the water soluble

hormone who's the second messenger you

have many choices that's the action do

you remember this beautiful chart yes we

are done with the intracellular

receptors these are the steroidal

hormones thyroid hormones vitamin d boom

we're done we're talking today about

what g protein coupled receptors which

are the most important cell surface

receptors when the hormone is water

soluble or hydrophilic the receptor has

to be on the cell surface we have three

types g-protein-coupled receptor by far

the largest and the most significant

family ligand-gated ion channels and

enzyme-length receptors now let's talk

about the g-protein-coupled receptor

g-protein-coupled receptors the largest

family of cell surface receptors no

kidding the action of those g protein

coupled receptors depend on three

factors number one the receptor number

two the g protein itself number three

the effector molecules the second

messenger systems the actual freaking

action tell me about this ligand oh

right this ligand is a hydrophilic

hormone something that's water soluble

thank you can you give me example of

these water soluble molecules sure it

could be catecholamine such as

epinephrine norepinephrine dopamine say

thank you to your adrenal medulla could

be acetylcholine oh yeah you see

sympathetic and parasympathetic awesome

glucagon to raise your blood sugar

serotonin to make your brain happy

secretin a hormone that secretes and

pituitary hormones such as tsh acth fsh

and lh tsh is stimulating the thyroid

gland acta stimulating the adrenal

cortex fsh and lh are submitting the

gonads thyroid gland adrenal cortex

gonads these are the three employees the

three glands that obey the pituitary but

homo medicosis haven't you said that the

three glands that obey the pituitary

secrete lipid-soluble hormones that's

true the glands themselves secrete

lipid-soluble hormones but these glands

get stimulated by pituitary hormones

that are water-soluble big difference so

tsh acth fs8 and lh are water soluble

however thyroid hormone t3 and t4

cortisol aldosterone testosterone

estrogens and progesterone these are

lipid soluble we're done with the ligand

tell me about the receptor this receptor

has seven trans membrane helices you

know a helix yeah you have seven of

these making the receptor a very complex

three-dimensional structure but just

let's keep it simple and we'll do seven

healthy right there look at this one

two three four five six seven talk to me

about the outer surface of the or the

outer region of the receptor well the

outer part is extra extracellular no

kidding and it's the binding site of the

ligand which is a water-soluble molecule

thank you tell me about the inner

surface the inner surface of the

receptor is intracellular of course is

the binding site of the g-protein

thank you and after the g protein what

do we got here the effector molecules

which are three gq gs or gi so we have

seven transmembrane helices and three

intracellular effector molecules they

are intracellular but they are still

bound to the inner surface of the cell

membrane okay mitochosis now i know

about the ligand now i know about the

receptor tell me about the g protein

your wish is my command the g protein g4

guanine nucleotide binding protein what

do you mean by guanine nucleotide i mean

either gtp or gdb this g protein will

bind gdb when the g protein is inactive

but when the g protein gets activated

it's gonna bind to the gtp because it

has an extra phosphate group how can the

gdp become gtp just acquire a phosphate

group but how will the gtp become gdp

destroy a phosphate group break down a

phosphate from it how do i break it down

hydrolysis what's the name of the enzyme

gt phase which broke down the gtp when

you convert gtp into gdp this is

converting the active g protein into an

inactive g protein and that's why gt

pays terminates the activity of the g

protein all right let me tell you about

this g protein has a trimeric protein

structure three subunits alpha subunit

which is the story beta subunit and

gamma subunit and the story of the g

protein looks like this the g protein

was inactive which means bound to gdp

suddenly it decided to become active how

did it decide well a soluble particle

came and bound to the receptor now the g

protein is active when it's active it's

gonna ditch that gdp and it's gonna bind

gtp gtp will activate the alpha subunit

when the alpha subunit gets active it

will kick the beta and the gamma subunit

away from it and the alpha will remain

alone alone in an active form who will

end the alpha subunit's entire career gt

pays because it breaks down the gtp into

gdp what's the function of the beta

subunit it just forms a complex with the

gamma subunit what's the function of the

gamma subunit it forms a complex with

the beta subunit this structure is

anchored to the cell membrane via a

lipid anchor because the cell membrane

is made of lipid activation of the g

protein first this water soluble

hydrophilic extracellular ligand is

going to bind to the receptor thank you

the receptor will undergo a

conformational change its

three-dimensional structure is gonna

change in shape this activated receptor

is gonna bind to the g protein which is

an intracellular structure when g

proteins becomes active it's gonna bind

gtp instead of gdp when you're buying

gtp when you are active alpha subunit is

gonna kick the beta and gamma complex in

the teeth get away from me i am active

eagles fly alone and when the alpha

subunit is active it's going to activate

the effector molecules gq gs or gi

that's the story of activation who will

end this activation process who will end

the alpha subunit's career this is the

gt phase because it breaks down gtp into

gdp and phosphate i hope that you know

that atp can be converted to click amp

via adelaide cyclase enzyme you can take

the cyclic emp to the cleaners by

phosphodiesterase enzyme which converts

cyclic mp into inactive metabolites or

degradation products or basically pieces

of trash absolute rubbish who stimulates

adenolate cyclase gs coupled receptor

who inhibits adelaide cyclase gi coupled

receptor s stands for stimulation i

stands for inhibition no duh how can we

inhibit the phosphodies trace enzyme by

a phosphodiesterase inhibitor in other

words there are two mechanisms by which

you can increase the level of cyclic mp

the first method is to boost the

activity of adelaide cyclase by gs

coupled receptor the second way to

increase cyclic emp is to destroy the

phosphodius trace so that no one will

take me to the cleaners so that the

level of cyclic mp will rise so if you

leave it to gs coupled receptors you

will have more cyclic amp if you leave

it to gi you will have less cyclic mp if

you give a phosphodiesterase inhibitor

you'll have more cyclic emp when you

write cyclic amp make sure the c is

lowercase because this has a completely

different meaning you know the saying

health books are the only books that can

kill you because of a typo you should

also grasp the fact that when an enzyme

is called kinase it's usually gonna add

a phosphate but when the enzyme is

called phosphatase it's gonna remove a

phosphate let's do it again the water

soluble hormone is now bound to the

receptor protein and then when this is

active i can activate the g protein

alpha will fly alone beta and gamma will

make a complex and get out of here alpha

is active to do what to activate gs gq

or gi when the g protein was inactive it

was like this bound to gdp and these

three were together but look at here

look when it's active when it's active

different things will happen but first

of all who activated the g-protein the

binding of the water-soluble hormone to

the receptor a conformational change

will happen to this receptor now the

g-protein is active and it's going to

bind gtp

instead of gdp the alpha subunit is now

active and it's going to kick the beta

gamma complex in the teeth get out of

here alpha subunit is active to do what

to activate gq gs or gi depending on the

situation gq will do what when you

activate gq you'll activate

phospholipase c which will increase

calcium gq

calcium also think of gq magazine very

muscular dudes when you activate gs it

will activate at a late cyclase more

cyclic emp when you activate gi it's

going to inhibit adelaide cyclase less

cyclic amp when i am inactive i am bound

to gdp who did this the jt pays gt pays

destroyed the gtp and now you have gdp

when you're buying gdp you are inactive

and you are inactive because the water

soluble hormone is detached but when you

are active the water soluble hormone is

attached and the gdp is becoming gtp by

acquiring an extra phosphate group pause

and review if you have watched the last

video what did we say we said that alpha

1 m1 m3 m5 h1 v1 and others are gq

coupled gq meaning phospholipase c and

therefore calcium contraction of smooth

muscles vasoconstriction

bronchoconstriction uterine contractions

all kinds of smooth muscle contraction

that's why oxytocin is gq coupled

because it increases uterine wall

contraction and the uterus has smooth

muscles that's why angiotensin ii is gq

coupled because it causes

vasoconstriction of blood vessels again

contraction of smooth muscles that's why

the v1 receptor of adh is gq coupled

because it causes vasoconstriction how

about the gs coupled receptors remember

your sympathetic stuff especially the

betas beta 1 beta 2 beta 3 because the

alpha is here alpha 1 is gq coupled

alpha 2 is gi because it's inhibitory

alpha 2 is an sob alpha 2 is

anti-sympathetic but the betas all of

them are gs coupled therefore activate

adelaide cyclase converts atp into

cyclic mp activates protein kinase a

everything here is a adelaide cyclase

atp cyclic amp protein kinase a to do

what increase the contraction of the

heart increase cardiac contractility

and vasodilation so i relax smooth

muscles unlike the calcium story

phospholipase

contracts smooth muscles but protein

kinase a

relaxes smooth muscles bronchodilation

vasodilation what's the opposite of

uterine contractions it's called

tocolysis which is relaxation of uterine

smooth muscles moreover beta 1 will

increase renal secretion also increase

aqueous humor secretion in the eye let's

do the g protein story one more time a

water soluble hormone is now bound to

the receptor let's talk about gs make

this about gs okay

this is active right g protein when it's

active is going to bind gtp alpha

subunit is going to dissociate from the

beta gamma complex alpha alone will

activate adelaide cyclase enzyme which

converts atp into cyclic amp cyclic amp

activates protein kinase a when i'm

called a kinase what's the function i

will add a phosphate this is the enzyme

before the kinase this is the enzyme

after the kinase it has acquired a

phosphate and therefore became active

most of the time here's the transporter

before the protein kinase a but here's

the transporter after protein kinase a

protein kinase a adds a phosphate

therefore the transporter is active most

of the time receptor becomes receptor

phosphate transcription factor becomes

transcription factor phosphate ion

channel becomes ion channel phosphate

structure protein structure protein

phosphate i converted everything from

inactive to active i am the protein

kinase a but hey where did you get the

phosphate group from easy i got it from

the gtp that's why the active form of g

protein always binds gtp and not gdp

because i need this extra phosphate to

activate all kinds of stuff all right

how can we go from the active state back

to the inactive state easy the cyclic mp

is gonna be taken to the cleaners thanks

to phosphodiesterase enzyme and the

protein kinase a will not be active

instead you will activate a phosphatase

what does a phosphatase do remove the

phosphate the enzyme phosphate will go

back to become an enzyme transporter

phosphate will become a transporter and

so and so forth basically converting the

active form into the inactive form this

was the story of the g protein it's a

very simple concept it's just your work

professor cannot teach do you remember

the sympathetic nervous system yeah we

had many sympathetic receptors including

alpha-1 which is gq you know why because

it needs to constrict blood vessels

calcium contraction of smooth muscles

how about alpha 2 alpha 2 is

anti-sympathetic because when you

stimulate the alpha 2 it decreases

norepinephrine it's anti-sympathetic

when something inhibits its gi because i

is inhibitory how about the betas the

betas are gs because i need to relax the

vessels relax the uterus but increase

cardiac contractility i also need to

secrete more renin and more icus humor

let's talk about the muscarinic

receptors of parasympathetic easy m1 m3

and m5 the odd numbers want to contract

stuff contract smooth muscles and

contract the asanas of the gland to

secrete stuff because this is secreto

motor parasympathetic therefore when you

want to contract smooth muscles you

better be gq to increase the calcium but

how about m2 and m4 i want to inhibit

everything gi the odd numbers are gq the

even numbers are gi the functions make

perfect sense pause and review but hey

medical says why is this so important

take it easy my friend take it look at

this sympathetic nervous system secretes

norepinephrine right yeah i know this

norepinephrine on the bladder what did

it do it relaxes the wall and constricts

this fainter because i was running from

a tiger relaxation and contraction are

two different functions how come one

ligand produces two opposite functions

because the receptor is different and

the g protein coupled receptor is

different if you want to relax the wall

of a smooth muscle you better be gs if

you want to contract a smooth muscle you

better be gq to increase the calcium it

makes sense how about the

parasympathetic nervous system is

acetylcholine wants to calm the heart

down how do i calm someone down gi is

inhibitory that's why it's m2 it has to

be an even number i want to contract the

walls of this bladder to get the urine

out m3 gq coupled gq calcium contraction

of smooth muscles i want to squeeze

those gastric glands because i am

secreto motor m3 is gq coupled gq

calcium constriction what does your

posterior pituitary gland release adh

and oxytocin who synthesized these two

hormones the prescription heck no it was

the hypothalamus and we talked about why

in previous videos in this endocrinology

playlist what's the only function of adh

to maintain your blood pressure to

prevent your blood pressure from

dropping so let's say that you were

walking down the street distracted with

your phone and then you got hit by a car

and lust lots of blood

if we leave you alone you will die from

hypotension but thankfully there is adh

coming to try to save the day adh has

one function in life to prevent your

blood pressure from dropping to maintain

a robust blood pressure let's go adh is

gonna do this by two receptors v1 and v2

why v because it's a vasopressin

vasopressin what do you think will do to

the vessels of vasoconstriction press

them constrict them how do i do this v1

receptor will do this for you how about

v2 v2 goes to the kidney and gets the

water out reabsorbs the water so that

the water goes back to the blood when we

increase the amount of volume in your

blood will increase the venous return

and therefore increase the preload and

increase the cardiac output and will

increase the blood pressure preventing

hypotension now take a wild guess if v1

wants to constrict vessels does it need

gq gs or gi oh that's easy of course gq

because gq calcium contraction of smooth

muscles how about dilating those

beautiful collecting tubules and get the

water out oh dilation relaxation of

smooth muscles cyclic mp therefore gs

coupled it's so easy tell me about

dopamine there is d1 receptor and d2 d1

activates the direct pathway d1 dilates

renal vessels mesenteric vessels as well

d2 inhibits so when d1 activates do you

think it's gs gq or gi and when g2

inhibits what kind of g-protein does it

need well it has to be s for stimulation

and i for inhibition also gs increases

cyclic mp which dilates and relaxes

smooth muscles see medicine makes so

much sense once you understand what the

flip you're talking about it's so simple

and easy there is no need to invent some

woke mnemonics to remember these just

think about it the best mnemonic is

understanding histamine h1 wants to

bronch a constrict h2 wants to increase

gastric acid secretion and of course you

cannot secrete without vasodilation

because you get those secretions from

the blood vessels and therefore h1 is gq

coupled h2 is gs coupled

to be continued in the next video don't

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happy study hard this is medicos's

perfect scenarios where medicine makes

perfect sense