GPCR basics

Question 1

GPCRs are

Answer 1

7 transmmemrbane receptors, which sense molecules on the outside of the cell and activate inside signal transactions pathways and cellular responses

Question 2

ligands

Answer 2

hormones, NT, light sensitive compounds

Question 3

3 families of GPCR

Answer 3

A, B, C

Question 4

A-

Answer 4

rhodopsin- sensitive to light, activates G protein transducer Gt to activate the hototransduction pathway

Question 5

B-

Answer 5

secretin/ glucagon receptor family e.g. peptide hormones

Question 6

C-

Answer 6

metabotropic glutamate family e.g. GABAA and glutamte

Question 7

mGluRs….

Answer 7

• modulation of synaptic transmission and neuronal excitability throughout the CNS
• high levels in cerebellum and thalamus

Question 8

Group 1 mGlu receptors

Answer 8

couples to PLC and intracellular calcium signalling

Question 9

activity of G proteins is regulated by

Answer 9

factors which control their ability to bind to and hydrolyse GTP to GDP

Question 10

when GTp is bound

Answer 10

on

Question 11

when GDP bound

Answer 11

off

Question 12

G proteins are activated by

Answer 12

GPCR

Question 13

G proteins are made up of

Answer 13

alpha, beta and gamma subunits ( beta-gamma complex)

Question 14

activation of G proteins process

Answer 14

• When GPCR binds to a signal molecule, the receptor is activated and changes shape, thereby allowing it to bind to an inactive G protein
• When this occurs, GTP displaces GDP which activates the G protein
• After transduction the G protein functions as a GTPase and hydrolyses the bound GTP which causes a phosphate group to fall off
• Regenerating GDP and inactivates G protein and the cycle repeats

Question 15

GalphaS controls which pathway

Answer 15

the cAMP dependent pathwat

Question 16

GalphaS and the cAMp dependent pathway

Answer 16

1)Gs alpha subunit stimulated G protein complex exchanges GDP to GTP and is released form the complex
2) the activated Gs alpha submit binds to and activates adenyl cyclase, which catalyses the conversion of ATP to cAMP
3) this increases in conc of the second messenger cAMP leads to activation of PKA
4) PKA enzyme is only activated when cAMP is present
5)

Question 17

responses mediated by cAMP

Answer 17

heart rate, cortisol section, breakdown of glycogen and fat

Question 18

PKA

Answer 18

protein kinase A

Question 19

protein kinase A is also known as

Answer 19

cAMP dependent enzyme because it gets activated only when cAMP is present

Question 20

cAMP pathways can..

Answer 20

activate enzymes and emulate gene expression (if this pathway is not controlled, it may lead to hyper-proliferation, which can contribute to cancer)

Question 21

GalphaI mainly

Answer 21

inhibits cAMP dependent pathway by inhibiting adenylate cyclase activity, decrease

Question 22

GalphaI

Answer 22

1) when Gi gets activated they release activated G-protein beta-gamma submits from inactive heterotrimeric G protein complexes
2) Gbeta-gamma interacts with GIRK channels to open them
3) they become more permeable to K+
4) hyperpolarization of the cell

Question 23

GIRK

Answer 23

gated, inwardly rectifying potassium channels

Question 24

GalphaI receptors mainly found

Answer 24

on the heart and the brain

Question 25

opioids target

Answer 25

GalphaI

Question 26

GalphaQ is involved in

Answer 26

activation of phospholipase C (PLC)

Question 27

GalphaQ

Answer 27

1) Gq activates PLC
2) PLC hydrolyses PIP2 to IP3 and DAG
3) DAG is a second messenger which activates PKC
4) IP3 acts on calcium channels to release calcium from store dn phosphorylation of some proteins

Question 28

GalphaQ receptors (7)

Answer 28

• serotonergic receptors
• Alpha-1 adrenergic receptors
• Vasopressin type 1 receptors
• Angiotensin II receptor type 1
• Histamine
• mGluR- Group 1
• M1, M2,M3 muscarinic receptors

Question 29

Summary of Gs

Answer 29

receptors:
-beta adrenergic receptors, glucagon, histamine, serotonin
singling pathway
- increase adenyl cylase
- increase in cAMP
- excitatory effect

Question 30

Summary of Gi

Answer 30

receptors:
- alpha2 adrenergic receptors
-mAchR
-opiopd
-serontin
Singling pathway
- inhibits adenylyl cycle 
-decrease in cAMP
- opens GIRK channels (cardiac K+ channels)
-hyperpolarisation
-decrease in heart rate

Question 31

Summary of Gq

Answer 31

receptors:

• mAchR
• serotonin

signaling pathway:

• activation of PLC
• PIP2- IP3 and DAG (PLC activation)
• increase in ca2+