Complexity in agonist actions: "signal amplification", "spare receptors", "receptor reserve"

Question 1

Because of “signal amplification “by downstream receptor signaling pathways, _____.

Answer 1

full receptor occupancy by agonists is seldom required for maximal responses

Question 2

Define spare receptors or receptor reserve.

Answer 2

Cells generally have more receptors than needed to generate maximal downstream responses.

Question 3

Consequences of spare receptors:

Answer 3

• dose-response curves for receptor EFFECTS are shifted to LEFT from dose-response curves for receptor occupancy
• the EC50 for drug response is often lower than the Kd for drug binding to the receptor
• drug effects can be more potent than would be expected from their binding affinity

Question 4

Importance of spare receptors:

Answer 4

1. allow cells to respond to very low concentrations of endogenous mediators
2. cells can lose some of many of their receptors but still generate full responses

Question 5

Agonist potency is high with spare receptors.

Answer 5

TRUE

Question 6

When curve shifts to the left, what happens to EC50 and spare receptors?

Answer 6

EC5) is a lower value; there are more spare receptors