Drug Receptors (1)

Question 1

What is meant by K_d ?

Answer 1

This is the equilibrium dissociation constant, and it refers to a drug’s affinity for a receptor. K_d = the drug concentration at which receptor occupancy is half-maximal (50% saturation of the receptors). K_d is inversely proportional to the affinity of the drug for the receptors.

Question 2

What is meant by EC₅₀ ?

Answer 2

EC₅₀ = the concentration of a drug at which there is 50% of the maximal drug effect (or “response”). Drugs with a higher EC₅₀ have a lower potency.

Question 3

What does it mean if there are “spare” receptors?

Answer 3

Receptors are said to be “spare” for a given pharmacologic response if it is possible to elicit a maximal biologic response at a concentration of agonist that does not result in occupancy of the full complement of available receptors.

Question 4

Give an example of an agonist and a receptor whereby there are receptors that are *temporally *spare, or “spare in time”.

Answer 4

Catecholamines and Beta-adrenoceptors on heart muscle. A maximal inotropic response of the heart muscle can be produced even when 90% of the receptors are blocked.

Question 5

What is meant by E_max ?

Answer 5

E_max is the maximum effect that can be produced by a drug. A drug with a higher E_max has a greater efficacy.

Question 6

Name the five categories of transmembrane signaling mechanisms (different ligand-receptor mechanisms)

Answer 6

1. Intracellular Receptors (for lipid-soluble ligands)
2. Transmembrane Enzymes (ligand binds to extracellular domain, and activates the enzymatic activity to occur at the cytosolic domain)
3. Transmembrane Receptors bound to a separate tyrosine kinase on the cytosolic domain
4. Ligand-gated and Voltage-gated ion channels
5. G-protein-linked receptors

Question 7

Give an example for each of the 5 categories of transmembrane signalling mechanisms (ligand-receptor mechanisms)

Answer 7

1. Corticosteroids to intracellular receptors.
2. Insulin to a transmembrane enzyme (a tyrosine kinase receptor).
3. Growth hormone binds to transmembrane receptor linked to a separate tyrosine kinase.
4. Acetylcholine binds to a ligand-gated Na⁺ channel
5. Catecholamines bind to Beta-adrenoceptors.

Question 8

Name three different types of G-proteins in G-protein-linked receptors.

Answer 8

G_s, G_q, G_i

Question 9

What does it mean if receptors are temporally spare, or “spare in time” ?

Answer 9

This means that the coupling of the agonist to the receptor produces an effect that lasts longer than the coupling itself. Even after the agonists have become uncoupled from the receptors (leaving the receptors unoccupied and thus “spare”), you may still see a maximal response being produced.