GPCRs As Drug Targets

Question 1

Basic G Prot Cycle

Answer 1

Inactive bound to GDP
R is GEF
Active bound to GTP

Question 2

GPCR Desensitization

Answer 2

Prolonged stimulation -> GRK phosphos -> arrestin binds -> inactivation and internalization

Question 3

Non-G Prot Signalling from GPCRs

Answer 3

Arrestin recruits Src, a tyr kinase, leading to gene transcription

Question 4

Nephrogenic Diabetes Insipidus (NDI)

Answer 4

V2R muts can’t make it to surface, so nonpeptidic-antagonists which act IC can restore proper folding and maturation to increase cell surface expression rather than influencing its signaling