Session 7

Question 1

What do cells require in order to respond to extracellular signalling molecules?

Answer 1

Receptors

Question 2

What are three types of receptors?

Answer 2

• Ligand-gated ion channel (nicotinic acetylcholine)
• Receptors with intrinsic enzymatic activity (insulin receptors)
• G protein coupled receptors (muscarinic acetylcholine receptors)

Question 3

What is the function of g protein coupled receptors?

Answer 3

• Muscle contraction
• Stimulus-secretion coupling
• Catabolic and anabolic processes
• Light, taste and smell perception

Question 4

What is the structure of a g protein coupled receptor?

Answer 4

• Heterotrimeric alpha, beta and gamma subunits

* Beta and gamma bind together and function as a single subunit

Question 5

How do g protein coupled receptors work?

Answer 5

1. The alpha subunit has a guanine nucleotide binding site which binds GTP and slowly hydrolyses it to GDP
2. Receptor activation leads to GDP being released from the alpha-subunit and GTP binding in its place
3. Binding of GTP decreases the affinity of the alpha subunit for the receptor and the beta-gamma subunit
4. Both the alpha and the beta-gamma subunits are released and can interact with effectors
5. Effector interaction is terminated by the intrinsic GTPase activity of the alpha subunit > GTP hydrolysed to GDP
6. Affinity of the alpha sub-unity for the beta-gamma subunit increases
7. The alpha-beta-gamma subunit is reformed and awaits reactivation by an agonist-activated receptor to re-initiate the cycle

Question 6

What effect does the pertussis toxin have on g-protein coupled receptors?

Answer 6

• Contains an enzyme which chemically modifies and inactivates Gi type proteins – thus uncoupling the receptor-effector linkage

Question 7

What effect does the cholera toxin have on g-protein coupled receptors?

Answer 7

• Contains a similar enzyme activity which modifies Gs type proteins
• Leads to irreversible activation – heterotrimeric unit is not reformed

Question 8

What is adenylyl cyclase?

Answer 8

• An integral plasma protein which can either be activated by Gs or inhibited by Gi via the activation of different receptors

Question 9

Give an example of a situation in which adenylyl cyclase is activated?

Answer 9

By noradrenaline at beta-adrenoreceptors

Question 10

Give an example of when adenylyl cyclase receptors are inhibited?

Answer 10

At alpha 2-adrenoreceptors

Question 11

What does adenylyl cyclase do in cells?

Answer 11

1. The enzyme hydrolyses cellular ATP to generate cAMP
2. cAMP then interacts with protein kinase A
3. PKA then phosphorylates a variety of other proteins within the cells to affect (either positively or negatively) their activities

Question 12

What does increased cAMP cause in cells?

Answer 12

• Increased glycogenolysis and gluconeogenesis in the liver
• Increased lipolysis in adipose tissue
• Relaxation of a variety of types of smooth muscle
• Postive inotropic and chronotropic effects in the heart

Question 13

What is phospholipase C?

Answer 13

• The effector enzyme in the signalling pathway involving the hydrolysis of PIP2 to InsP3 and DAG