G protein coupled Receptors

Question 1

G protein-coupled receptor structure

Answer 1

N terminus on outside, 7 connected helical transmembrane (1-7) domains that form a circle together, intracellular domains: i2 loop between 3-4, i3 loop between 5-6 (bigger loop), C terminus on inside of cell. Transmembrane and/or extracellular domains are ligand binding, intracellular are G protein coupling

Question 2

activation of hetero-trimeric G proteins

Answer 2

ligand binds => GDP dissociates from alpha-beta-GTP complex => GTP binds to form active G protein => alpha and beta subunits dissociate to cause downstream effects. Alpha is GTPase => GTP to GDP to return to inactive state.

Question 3

PLC

Answer 3

alpha-1-AR binds NE, epi, or phenylephrine => PLC cleaved by Gq-alpha subunit => IP3 and DAG => IP3 binds receptor in ER => releases calcium, DAG binds PKC => Ca influx into cell => decreased blood flow to skin, increased BP

Question 4

cAMP

Answer 4

beta-1-AR binds NE, epi, or isoproterenol => Gs-alpha subunit activates AC => cAMP produced => activates protein kinase A (PKA) => Ca cannels open (influx => increased heart rate and contraction

Question 5

receptor desensitisation

Answer 5

same time pathway is activated, another is activated that favors desensitisation. Beta activated GRK kinase => phosphorylates receptor => attracts beta arrestin => prevents association of another g-protein => beta arrestin interacts with clathrin => receptor is endocytosed => internalized receptor can be resensitized or sent to lysosome

Question 6

beta blockers

Answer 6

prevent activation of a pathway (antagonists) and decrease heart rate. Metoprolol prevents cAMP production

Question 7

alpha blocker

Answer 7

prazosin antagonist of alpha-1-AR receptor. Prevents IP3 and DAG production, decreases blood pressure