Receptor-Effector Signalling Via G Proteins -- 7.1

Question 1

Why is signal transduction needed?

Answer 1

Generate a response inside the cell after an effector binds to an extracellular receptor.

Question 2

What receptor does adrenaline/noradrenaline bind to and what effects does it have?

Answer 2

B-adrenoceptor
Stimulates adenylyl cyclase
Causes glycogenolysis and lipolysis

Question 3

What receptors does acetylcholine bind to and what effects does it have?

Answer 3

M3 – Gq protein
Stimulates phospholipase C
Causes smooth muscle contraction

M2 – Gi protein
inhibits adeylyl cyclase and stimulate K+ channels
Slows the cardiac pacemaker

Question 4

What receptors does light have an effect on and what effects does it have?

Answer 4

Rhodopsin receptor – G alpha T transducin
Stimulates cyclic GMP phosphodiesterase
Causes visual excitation

Question 5

What does phospholipase C cause?

Answer 5

Causes hydrolysis of PIP2 to generate inositol 1,4,5 - triphosphate and diacylglycerol (InsP3 and DAG)

Question 6

What G protein does rhodopsin activate and what effects does it have?

Answer 6

Activates G protein called transducin

This activates a phosphodiesterase enzyme which hydrolyses cGMP to 5’GMP

Question 7

Name two types of drugs which are G protein agonists and the receptors they bind to

Answer 7

B adrenoceptor agonist e.g. Salbutamol/Salmetrol as anti-asthma drugs

μ-opioid receptor agonists e.g. Morphine/Fentanyl as analgesia or anaesthetics

Question 8

Name two type of drugs that are G protein antagonists and the receptors that they bind to

Answer 8

β adrenoceptor antagonists e.g. Propranolol and Atenolol as cardiovascular drugs fro hypertension

D2 dopamine receptor antagonists e.g. Haloperidol and Sulpiride as neuroleptics/ anti-schizophrenic

Question 9

What is the common basic structure for G proteins?

Answer 9

• Single polypeptide chain (300-1200 amino acids)
• 7-transmembrane (7TM)- spanning regions
• Extracellular N-terminal
• Intracellular C-terminal

Question 10

What two regions of GPCRs are responsible for receptor binding?

Answer 10

• • Is formed by 2/3 of the transmembrane domains

- - N terminal region or other extracellular domains

Question 11

Describe the process of signalling by a G protein

Answer 11

1. Receptor is activated by binding of substrate
2. Activated receptor has a high affinity for GDP-G protein. Binding of this causes GDP to be exchanged for GTP.
3. Alpha-GTPs affinity for receptor and beta/gamma subunit lowers so alpha-GTP and beta/gamma subunit can now interact with effectors.
4. GTPase terminates alpha-GTP reaction, heterotrimer is reformed and awaits reactivation.

Question 12

How is the length of effector/G-protein interaction determined?

Answer 12

By GTPase activity.

This may be regulated by RGS proteins

Question 13

What can the activated receptor be called in the G-protein activation reaction?

Answer 13

Acts as a guanine exchange factor

Question 14

How does the cholera toxin interfere with G protein function?

Answer 14

It contains an ADP-ribosyl transferase enzyme which inactivates alpha Gs subunits, leading to irreversible activation by preventing GTPase activity.

Question 15

What does the interference of the cholera toxin cause?

Answer 15

It causes cAMP production and H2O, K+, Na+, Cl- and HCO3- into the lumen of the small intestine, causes diarrhoea and dehydration

Question 16

How does the pertussis toxin interfere with G protein function?

Answer 16

It contains an ADP-ribosyl transferase enzyme which inactivates Gi proteins