G-Protein-Coupled Receptors

Question 1

Classes & Types of GPCRs

Answer 1

Class A: Rhodopsin receptor family
Class B: Secretin receptor family
Class C: Metabotropic glutamate receptor like family

GS: Stimulatory, increased cAMP
Gi: Inhibitory, less cAMP
Gq: Stimulatory
G12: Effects on cytoskeleton, actin, cell migration, survival & plasticity

Question 2

Structure of GPCRs

Answer 2

7 transmembrane domains in form of 6 loops

Question 3

GPCR signaling

Answer 3

Receptor bound to G protein complex in inactive state
Binding of agonist → Conformational change → Transmitted to Galpha subunit = Activation → Exhange of GDP to GRP → Dissociation of Galpha from the Gbeta/gamma dimer
Galpha: Adenylyl cyclase activation → cAMP → Protein kinases activation
Gbeta/gamma: Activation of GRIK channels → K+ efflux → Rather inhibitory

Question 4

Main targets of GPCRs

Answer 4

Adenylyl cyclase → cAMP → Protein kinases
Phospholipase C/IP3/DAG → Gq → Increase free Ca2+ → Activates PKC
Phospholipase A2: Formation of arachnoid acids & eicosanoids → Opening of K+ channels & inhibiting Ca2+ channels

Question 5

Dopamine receptors

Answer 5

D1: DR1 (Golf), DR5 (Gs)
D2: DR2, DR3, DR4 - coupled to Gi

Question 6

GABA-B

Answer 6

Dimer → Inhibits cAMP & opens GIRK (K+ efflux) → Inhibition
Structure: Ec venus flytrap (VFT, contains GABA binding site) & ec sushi domain → Binding of GABA to GB1, G-protein is coupled to GB2

Question 7

Adrenergic receptors

Answer 7

Alpha1: Coupled to Gq
Alpha2: Coupled to Gi
Beta1,4,3: Coupled to Gs

Question 8

Serotonin receptors

Answer 8

5-HT1&5: Coupled to Gio
5-HT4&6&7: Coupled to Gs
5.HT2: Gq/11
5-HT3: Ionotropic - permeable for Na+ & K+
5-HT2R: Ionotorpic, Cys-loop receptor, cation selective

Question 9

Muscarinic Acetylcholine receptors

Answer 9

M1-like: M1,M3,M5 → Gq
M2-like: M2 & M4