Intracellular Signalling- G Proteins

Question 1

Describe how G-Proteins in general produce a cellular response and how the response stops

Answer 1

1. GPCR activated by ligand
2. GDP is exchanged for GTP, activating G-protein
3. Alpha-GTP subunit and Beta-Gamma subunit formed
4. Send signals to effectors
5. GTPase removes Pi from Alpha-GTP—> Alpha-GDP
6. Alpha-GDP and Beta-Gamma recombine to form inactive G-protein

Question 2

Explain how Cholera Toxin and Pertussis Toxin affect G-Protein function

Answer 2

CTx: Stops GTPase function, so constant signals to effectors from Alpha s-GTP subunits

PTx: Stops GDP exchange for GTP, on Alpha-i subunits, so no Gi-protein activation

Question 3

Describe the function of Gs-Protein coupled receptors

Answer 3

1. GPCR activated
2. GDP exchanged for GTP-> GTP-Alpha s subunit produced
3. GTP-Alpha s activates Adenylyl Cyclase to make cAMP from ATP
4. cAMP stimulates PKA (Binds to R region, C subunits dissociate to phosphorylate target proteins)

Question 4

Describe the function of Gi-Protein coupled receptors

Answer 4

1. GPCR activated
2. GDP-Alpha i ————> GTP-Alpha i - subunit
3. GTP-Alpha i subunit inhibits Adenylyl Cyclase, so no cAMP

Question 5

Describe the function of Gq -Protein coupled receptors

Answer 5

1. GPCR activated
2. GDP-Alpha q———> GTP-Alpha q subunit
3. This subunit stimulates PLC, which hydrolyses PIP2->DAG + IP3
4. IP3 diffuses to + opens IP3 Receptors on ER, increasing Cytoplasm Ca
5. DAG moves along membrane, and with Ca, activates PKC
6. PKC phosphorylates its substrates

Question 6

Explain how Inotropy, Chronotropy and Vasodilation are affected by Adrenaline/ Noradrenaline?

Answer 6

1. Interact with Beta-1 receptors, activating Gs Proteins
2. Adenylyl Cyclase stimulated, more cAMP, PKA activated
3. PKA causes Vasodilation AND phosphorylates VOCC
4. VOCC activated, Ca enters cell-> (+)ve Inotropy, Chronotropy

Question 7

Outline the effects Noradrenaline and Acetylcholine on smooth muscle contraction

Answer 7

Noradrenaline interacts with Vascular Alpha-1 Adrenoceptors to cause Vasoconstriction

Acetylcholine interacts with Smooth muscle M3-Muscarinic receptors to cause Bronchoconstriction

Question 8

Describe the structure of a G-Protein?

Answer 8

Heterotrimer: 3 Subunits; Alpha, Beta, Gamma

Alpha-GTP bonded to Beta-Gamma, which function as a singular subunit

Question 9

Explain how Morphine affects Neurotransmitter release

Answer 9

Morphine activates GPCR
GTP-Alpha i subunit produced + Beta-Gamma subunit
Beta-Gamma inhibits VOCC—>Reduced Ca influx-> Reduced Neurotransmitter exocytosis