DONE GPCRs

Question 1

What is the 3 step overview for signal transduction?

Answer 1

Receptor –> G-protein –> effector

Question 2

GPCR structure

Answer 2

7 transmembrane spanning regions
Extracellular N-terminus (binding domain)
Or binding domain in transmem. domain
Intracellular T-terminus

Question 3

What does G protein mean?

Answer 3

Guanine nucleotide-binding protein

Question 4

What does G-alpha s activation cause?

Answer 4

Stimulation of adenylyl cyclase to catalyse conversion of ATP to cAMP
cAMP stimulates PKA (phosphorylates target proteins)

Question 5

What does G-alpha i activation cause?

Answer 5

Inhibition of adenylyl cyclase, no cAMP = no PKA

Question 6

What does G-alpha q activation cause?

Answer 6

Activates phospholipase C to catalyse conversion of PIP2 to IP3 and DAG
IP3 causes release of Ca2+ from ER
DAG binds to PKC = phosphorylation of proteins

Question 7

What receptor does adrenaline activate in positive inotropy?

Answer 7

Beta-1 adrenoceptor via G-alpha s pathway (cAMP forms PKA, which phosphorylates VOCCs = more Ca2+ from SR = more forceful contraction)

Question 8

What are the 3 processes that cause Ca2+ efflux from the cytoplasm?

Answer 8

PMCA (ATP hydrolysis drives from cyto. to extracellular)
SERCA (from cyto. to ER)
NCX (Na+ influx, Ca2+ efflux)

Question 9

Processes that cause Ca2+ influx?

Answer 9

LGICs (across mem.)
VOCCs (across mem. , due to depolarisation)
IP3 receptors (from ER lumen to cyto. by Gaq)
CICR (ryanodine receptors, cardiac ventricular cells, Ca entry into cyto = bind to CICR channels = release of ER Ca)

Question 10

Beta 2 adrenoceptor agonists

Answer 10

Anti-asthma = salbutamol

Question 11

Beta adrenoceptor antagonists

Answer 11

Treat hypertension = propanolol

Question 12

Cholera toxin

Answer 12

Prevents termination of signalling by G-alpha s = prevents GTPase activity = permanently on = intestinal cells release fluid

Question 13

Pertussis toxin

Answer 13

Uncouples Gi GPCRs from mediating signal transduction

So can’t lose GDP = pathway stops = can’t inhibit activity of adenylyl cyclase

Question 14

Inotropy in heart

Answer 14

Adrenaline/noradrenaline activate beta-1 adrenoceptor (G-alpha s)
Increase cAMP formation = binds to PKA
PKA phosphorylates VOCCs
Greater release of calcium from SR when mem. depolarises = more forceful contraction

Question 15

Arteriolar vasoconstriction

Answer 15

Noradrenaline, alpha 1 adrenoceptors
Stimulates phospholipase C via G-alpha q
Forms IP3 = calcium release from SR
DAG increases = activates PKC = phosphorylates smooth muscle = vasoconstriction

Question 16

Give an example of a GPCR and a ligand-gated ion channel

Answer 16

Muscarinic ACh

Nicotinic ACh

Question 17

Give an overview of how GPCRs work

Answer 17

Ligand binds to GPCR = conformational change
G protein activated, GDP exchanges for GTP on alpha subunit by GTPase
Alpha beta/gamma complex dissociates into alpha-GTP and free beta/gamma, interact with effectors (enzymes)

Question 18

If GTPase activity is reduced , what happens?

Answer 18

More time for signal transduction

Question 19

QISS QIQ

Answer 19

SYMPATHETIC , adrenergic
Q = alpha 1
I = alpha 2
S = beta 1
S = beta 2

PARASYMPATHETIC , mACh receptors
Q = M1
I = M2
Q = M3