ICPP S3 Specific Effector Mechanisms

Question 1

What are the 2 main enzyme effectors of G-proteins?

Answer 1

Adenylyl cyclase

Phospholipase C

Question 2

Describe agonist stimulation of adenylyl cyclase and how this produces the secondary messenger.

Answer 2

Agonist bind
Blah blah blah
alpha-GTP bind to AC stimulating it
AC converts ATP to cAMP
cAMP is the secondary messenger

Question 3

What will secondary messenger cAMP bind to and activate?

Answer 3

cAMP-dependant PKA
Epacs
Cyclic-nucleotide-gated ion channels (CNGs)

Question 4

Describe structure of PKA

Answer 4

Tetramer
2 regulatory subunits
2 catalytic subunits

Question 5

Describe interaction between cAMP and PKA.

Answer 5

2 molecules of cAMP bind to each regulatory subunit.
4 bind overall to one PKA.
Causing release of 2 catalytic subunits.

Question 6

Describe agonist stimulated inhibition of AC.

Answer 6

Agonist binds to Gai GPCR.
Blah blah blah
Alpha-GTP binds to AC inhibiting conversion of AC to cAMP.

Question 7

Where are Gs couple receptors found?

Answer 7

B-adrenoceptors
D1-dopamine receptors
H2-histamine receptors

Question 8

Where are Gi couple receptors found?

Answer 8

A2-adrenoceptors
D2-dopamine receptors
U-opioid receptors.

Question 9

Describe agonist-stimulated activation of PLC and secondary messenger generation.

Also describe how these secondary messengers go on to activate their relevant effectors.

Answer 9

Agonist binds to Gaq GPCR
Blah blah blah
alpha-GTP binds to PLC
PLC cleaves membrane phospholipid PIP2 to DAG and IP3.
DAG remains in the membrane.
IP3 binds to IP3 receptor causing Ca2+ release.
Ca2+ and DAG bind to PKC and prime it to catalyse its reactions.

Question 10

Where are Gq coupled receptors found ?

Answer 10

A1 adrenoceptors
M1 muscarinic receptors
H1 histamine receptors

USE QISS QIQ SIQ SQS

Question 11

How is inotropy of the heart controlled by B1-adrenoceptors?

Answer 11

Adrenaline from blood or NA from SNS can bind to Gas GPCR cause activation of AC and cAMP production.
cAMP activates PKA which will phosphorylation VOCC allowing calcium in.

Question 12

How is vasoconstriction controlled by a1-adrenoceptors?

Answer 12

NA release from SNS bind to Gaq GPCRs

Vasoconstriction through PLC pathway.

Question 13

How is bronchoconstriction controlled by M3 muscarinic receptors?

Answer 13

Parasympathetically released ACh binds to Gaq GPCRs

Uses PLC pathway.

Question 14

In the CNS and PNS what is NT release modulated by?

Answer 14

Presynaptic GPCRs

Question 15

How does u-opioid receptor modulate NT release?

Answer 15

Morphine for example will bind to u-opioid GPCR which is associated with the Gai protein.

After dissociation of the subunits has occurred the beta-gamma subunit will bind to a VOCC reducing Ca2+ influx and subsequent NT release.