M&R - G protein coupled receptors Flashcards
What do agonists at GPCRs do?
Bind to receptor and activate it
E.g B2 agonists - anti asthma
What is transduction?
A series of intracellular proteins that occur in series and bring about a cellular response
What do antagonists at GPCRs do?
Bind to receptors and do not activate it (block agonists)
E.g B - Antagonists treat hypertension
What are 3 genetic changes that can occur to GPCRs?
Retinitis pigmentosa- loss of function mutation to rhodopsin
Nephrogenic diabetes insipidus- caused by loss of function to vasopressin receptors
Familial male precocious puberty - caused by a gain of function mutation to LH receptor
What is the variety of stimuli that GPCRs respond to?
E.g ions (H+, Ca2+)
Neurotransmitters
Peptide and non peptide hormones
Large glycoproteins
How many CPCRs are in the human genome
865
What is the structure of G protein coupled receptors?
Single peptide with 7 transmembrane spanning domains
An Extracellular N terminal and an intracellular C terminal
Where are the 2 regions for ligand binding?
Between 2 or 3 of the transmembrane domains or in the N terminal region
Once the ligand is bounded to a G protein receptor what happens?
Induces a conformational change that is enough to activate a G protein
What are the 3 subunits that make up a G protein?
Aloha, beta, gamma
How is the G Protein activated?
The exchange of GDP for GTP on the alpha subunit
Once activated what happens to the subunits?
The alpha and beta-gamma complex dissociates the. Each interacts with effector proteins
How is the G protein signal terminated?
GTPase activity hydrolyses GTP back to GDP
The a - GDP and beta-gamma subunits then reform to the inactive heterotrimeric complex
What are the 4 types of G protein alpha subunit that acts on effectors?
Gs, Gi, Gq, Gt
What happens when adrenaline or NA acts on B adrenoceptors?
Gs alpha is activated and stimulates adenylyl cyclase activity
What happens when adrenaline or NA acts on a2 adrenoceptors?
Gi alpha subunit inhibits adenylyl cyclase
What happens when adrenaline or NA acts on a1 adrenoceptors?
The activates Gq alpha protein which stimulates Phospholipase C
Which G protein is activated by ACh binding to M1/M3 muscarinic receptors?
Gq alpha
What can effectors be?
Enzymes or ion channels
What are cAMP and IP3 and DAG?
2nd messengers
What reaction does adenylyl cyclase stimulate?
ATP —> cAMP
What enzyme does cAMP exert the majority of its action through?
Cyclic AMP - dependant protein kinase
How does cAMP- dependent PK act?
cAMP binds to the regulatory sites which in turn causes the catalytic sites to dissociate and phosphorylate target proteins in the cell
E.g VOCC in heart muscle (increasing contractility)
What does Phospholipase C do?
It catalysts the cleavage of phospholipid PIP2 into IP3 and DAG
IP3 activates receptors on the SR causing calcium influx whilst DAG activates PKC
