L1 - How do drugs work

Question 1

Factors that affect interaction between receptors and ligands

Answer 1

1. Specificity
2. Affinity
3. Saturation
4. Competition

Question 2

What is an agonist?

Answer 2

A ligand/chemical that when it binds to a receptor , it activates it to produce a biological response.

Question 3

What is an antagonist?

Answer 3

A ligand/chemical which blocks the receptor.

It has an affinity to the receptor but not efficacy so does not activate a biological response.

E.g. antihistamines, beta blockers

Question 4

What is down-regulation?

Answer 4

• Occurs in response to a chronically high concentration of ligand
• Decreases the sensitivity (desensitise) of the cell response to frequent or intense stimulation.
• Main mechanism - e.g. internalisation
• Internalisation - ligna-receptor complex taken into cell by receptor-mediated endocytosis

Question 5

What is up-regulation?

Answer 5

• An increase in the number of receptors on the surface of the target cells - sensitising to hormone/ligand
• Main mechanism - intracellular vesicles containing receptor proteins which fuse with plasma membrane, inserting receptor proteins into the plasma membrane

Question 6

Examples of signal transduction pathways

Answer 6

• Direct opening of ion channels
• Direct activation of an enzyme
• Indirect activation/inactivation of enzyme
• Indirect opening/closing of ion channel (involves G-proteins)

Question 7

Examples of receptor-operated ion channels and their targets

Answer 7

Opening of cation channels (mainly Na+):
- Acetylcholine (agonist)
- Nicotinic + cholinergic receptors

Opening of Na+ or Ca++ channels:
- Glutamate (agonist)
- Excitatory amino acids as receptors

Opening of Cl- channels:
- GABA (agonist)
- GABA(a) receptor

Question 8

Examples of tyrosine kinase receptors (enzyme-linked) and their targets

Answer 8

EGFR receptors:
- Epidermal growth factor (EGF) agonist
- Physiology -> proliferation, differentiation, cell survival
- Disease -> cancer

PDGFR receptors:
- Platelet-derived growth factor (PDGF) agonist
- Physiology -> proliferation, differentiation, development
- Disease -> cancer

Insulin receptors:
- Insulin hormone (agonist)
- Physiology -> glucose uptake
- Disease -> diabetes

Question 9

3 Examples of effector enzymes part of G-protein-coupled receptor signalling

Answer 9

1. Adenylyl cyclase:
   ATP —> cAMP
2. Phospholipase C:
   PIP2 —> DAG + IP3
3. cGMP phosphodiesterase:
   cGMP —> GMP

Question 10

Events activated via Ca++ signalling

Answer 10

• Cell proliferation
• Muscle contraction
• Neuronal excitability
• Metabolism
• Secretion