GPCR Flashcards
(38 cards)
What is the sympathetic nervous system?
Sympathetic nerves release noradrenaline.
Adrenal medullae release adrenaline and noradrenaline - catecholamines
What are the types of receptor which catecholamines binds?
a-adrenoceptors
b-adrenoceptors
What is the agonist potency order of a1 adrenoceptors?
Noradrenaline >adrenaline»isoprenaline
What is the agonist potency order of a2 adrenoceptors?
Adrenaline > noradrenaline»_space; isoprenaline
What is the agonist potency order of b1 adrenoceptors?
Isoprenaline > noradrenaline > adrenaline
What is the agonist potency order of b2 adrenoceptors?
Isoprenaline > adrenaline > noradrenaline
What is the agonist potency order of b3 adrenoceptors?
Isoprenaline > noradrenaline = adrenaline
What are adrenergic receptors?
Part of the family of G protein coupled receptors.
Recruit G proteins to produce cellular effects
Integral membrane protein
What is the structure of adrenergic receptors?
Single polypeptide chain.
Extracellular N-terminus, intracellular C-terminus (carboxylic acid end)
7 transmembrane a helices
Binding site buried within a cleft between the a helices
What is the specificity of G-protein coupled receptors?
a, and b-adrenoceptors recruit different intracellular G proteins.
So, a and B adrenoceptors utilise different intracellular messaging systems to produce their cellular effects.
The long third cytoplasmic loop is the region of the receptor that couples to the G protein.
What are G-protein coupled receptors?
Have 3 subunits - alpha, beta and gamma
When bound to receptor, it is in GDP form.
When an agonist binds, it causes the G protein to be phosphorylated and GDP forms GTP.
This makes the G protein unstable, so a-subunit dissociates from beta-gamma subunit and moves in membrane to act on target protein, to mediate effects in the cell.
What is the mechanism of a1 adrenoceptors on G-proteins?
a1 adrenoceptors are coupled to Gq proteins.
Noradrenaline binds to receptor, which phosphorylates Gq protein.
The a-subunit dissociates and activates phospholipase C, which acts on the phospholipid PIP2.
What are the effects of the a1 adrenoceptor?
PIP2 produces inositol triphosphate (IP3) and diacylglycerol (DAG).
IP3 releases Ca2+ from the endoplasmic reticulum, which will have an effect depending on the cell type - smooth muscle contracts, secretory organ secretes.
DAG activates protein kinase C, which phosphorylates proteins.
What is the mechanism of a2 adrenoceptors?
Noradrenaline binds to a2-adrenoceptors, which is coupled to Gi protein.
a-subunit binds to adenylyl cyclase, and inhibits it.
What is the effect of a2-adrenoreceptors?
Adenylyl cyclase is inhibited so it cannot convert ATP to cyclic AMP, so cAMP levels are decreased.
cAMP can not activate protein kinase A, so there is reduced activity of PKA.
Therefore there is reduced phosphorylation of proteins.
What is Yohimbine?
It is an antagonist that blocks the a2 adrenoceptor, so inhibits the inhibitory affect of the a-subunit, so amplifies sympathetic function.
What is the mechanism of B-adrenoceptors?
Noradrenaline binds to B-adrenoceptor, which is coupled to Gs protein.
The a-subunit binds and stimulates adenylyl cyclase.
This converts ATP to cAMP, which activates protein kinase A, so there is increased phosphorylation of intracellular proteins.
What is the relationship between a2 and B adrenoceptors?
They have an opposing effect.
a2 adrenoceptor effect on smooth muscle will cause contraction.
b adrenoceptor effect will cause relaxation.
What are the B1adrenoceptors that act on the heart?
Sino-atrial node - increased heart rate.
Atrio-ventricular node - increased conduction velocity.
Atria - increased contractility
Ventricles - increased contractiliity, enhanced automaticity.
How does the sino-atrial node increase heart rate?
Sympathetic nerves release noradrenaline which acts on the b1 adrenoceptors.
These activate the Gs pathway, and increases heart rate.
What are adrenoceptors in the smooth muscle?
Blood vessels - a1 causes constriction, b2 causes dilation
Bronchi - b2 dilation
GI tract - a1 and a2 contraction of sphincters, b2 relaxation.
Uterus - b2 relax
Adipose tissue - b3 lipolysis, thermogenesis.
What agonists act on adrenoceptors?
Phenylephrine on a1 adrenoceptors for cold remedies
Clonidine acts on a2 in brain
Dobutamine increases force of contraction on heart by b1 adrenoceptors.
Salbutamol for asthma on b2.
Mirabegron on b3.
What is isoprenaline?
A non-selective b-adrenoceptor agonist.
Where are the b adrenoceptors?
B1 receptors are in the heart, so drugs acting on b1 will affect the heart.
B2 are in the lungs.
B3 in bladder and fat.
