L05 - Receptors and membrane signalling

Question 1

What is affinity?

Answer 1

KD = binding strength

Question 2

What is efficacy?

Answer 2

Emax = maximum response achievable

Question 3

What are agonists?

Answer 3

Possess affinity and efficacy

- Bind to a receptor and produce a response

Question 4

What is potency?

Answer 4

A measure of drug activity - a highly potent drug is only required in a very small dose
- Therefore, potency is related to affinity

Question 5

Describe the relationship between drug conc and response

Answer 5

• Graded (even linear at the beginning)
• Saturating
• Exhibits threshold

(- Hyperbolic until Emax; sigmoid when log[agonist])

Question 6

What are super-agonists?

Answer 6

Highly efficacious agonists that can produce a maximal response from the cell without binding to all of the available receptors

Question 7

What is the action of goserelin (zoladex)?

Answer 7

Super agonist of the gonadotropin-releasing hormone receptor (GnRH-R)
- Suppresses production of the sex hormones (testosterone and oestrogen), particularly in the treatment of breast and prostate cancer

Question 8

What are partial agonists?

Answer 8

Low efficacy
- Partial agonists cannot produce the cell’s maximal response, even when they have bound to all of the available receptors

Question 9

What is the action of buprenorphine?

Answer 9

Partial agonist at particular receptor

• Opioid used to treat opioid addiction
• Moderate acute pain and moderate chronic pain

Question 10

How do steroid hormones work?

Answer 10

Bind to intracellular nuclear receptors

• Activate membrane-bound GPCR
• The result of steroids often result from interplay of the two mechanisms

Question 11

What are the two different possible doses of aspirin available and for what effects?

Answer 11

Two different dosings of the same drug is equivalent to two different drugs

• 75mg per day low dose aspirin acts as blood thinner
• 300mg-500mg as pain killer

Question 12

What are the different ways of regulating cell function?

Answer 12

1. Altered membrane potential
2. Altered enzyme activity
3. Altered gene expression
4. Most drugs affect cell function via (physiological) receptors
   - Act ‘hormone-like’ - an artificially made hormone molc may directly be used as a drug

Question 13

How are receptors classified?

Answer 13

Receptors are classified on the basis of the selective action of drugs
- Named according to the transmitter or hormone with which they interact (ACh receptors)

Question 14

What are the different receptor superfamilies?

Answer 14

1. Integral ion channels
   - Nicotinic receptor
   - Glycine receptor
2. Integral tyrosine kinases
   - Insulin receptor
3. Nuclear receptors = steroid receptors
   - Oestrogen receptor
   - Androgen receptor
4. G-protein coupled receptors
   - Muscarinic receptors (adrenoceptors)
5. Cytokine receptors
   - Prolactin receptor
   - GH TNF receptor

Question 15

Which structures could be drug receptors?

Answer 15

1. Enzymes
   - Cyclooxygenase
2. Ion channels
   - Ca2+ channels blocked by nifedipine
3. Transporters (pumps, transport proteins)
   - Noradrenaline transported blocked by cocaine
4. Physiological receptors
   - Receptors for hormones, NTs
   - ACh, histamine, insulin etc
5. Substrates, metabolites and proteins
6. DNA/ RNA and the ribosome
7. Various physiochemical mechanisms
8. Targets of monoclonal antibodies
9. Unknown mechanism of action (for many drugs)