Molecular Basis of Drug Interaction

Question 1

Gs

1. Receptors for…
2. Effectors/actions

Answer 1

Stimulatory

1.Beta-adrenergic amines, glucagon, histamine, serotonin, many hormones

2. Activates adenyl cyclase → ↑ cAMP
   

Question 2

Gi1, Gi2, Gi3

1. Receptors for…
2. Effectors/actions

Answer 2

Inhibitory

1. a2-adrenergic amines, acetylcholine (muscarinic), opioids, serotonin, others
2. Inhibits adenylyl cyclase → ↓ cAMP, activates cardiac K+ channels → ↓ heart rate

Question 3

Gq

1. Receptors for…
2. Effectors/actions

Answer 3

Stimulatory

1. Acetylcholine (muscarinic), bombesin, serotonin, others
2. Activates phospholipase C → ↑ IP3, DAG, intracellular Ca++

Question 4

Receptor Regulation mechanisms

Answer 4

phosphorylation, endocytosis, and proteolysis

Question 5

Short-term desensitization of G protein-coupled receptors

Answer 5

a) via phosphorylation of serine and threonine residues in the receptor by G protein-coupled receptor kinases (GRKs)
b) Phosphorylated residues prevent interaction with G proteins, receptor binds to b-arrestin instead → decreased signal b/c now even w/agonist receptor can’t bind G protein
c) Upon removal of agonist, phosphorylated serines and threonines are dephosphorylated by cellular phosphatases

Question 6

Long term desensitization

Answer 6

eceptors are trafficked to lysosomes and degraded