PD Principles: Effect of Drugs on Receptors & Cell Signaling; Regulation/Summary

Question 1

Mechanisms of receptor regulation:

Answer 1

Downregulation
• Reduce receptor number
• Attenuates response

Inhibition (antagonists)
• Blocking receptor function

Sequestration
• Receptors are internalized
• Degradation or recycling to surface
• Not accessible to ligand

Degradation
• Regulated receptor destruction

Question 2

Single transmembrane receptors:

Answer 2

Dimerize upon ligand binding but have different kinase activities.

Question 3

Transmembrane channels:

Answer 3

– React to either membrane potential or ligand binding

– Allow ion flux between extracellular space and cytosol

Question 4

7-transmembrane domain receptors (GPCRs):

Answer 4

– Bound to a trimeric G-protein
– G-protein bound to GDP is inactive, bound GTP is active
– Extensive downstream events and regulation