Emerging concepts in GPCR function--the influence of cell phenotype on GPCR pharmacology.
G protein coupled receptors (GPCRs) are an important class of ligand-activated proteins that regulate cellular metabolism. It is now appears that GPCR function is highly dependent upon the cellular environment in which it is expressed. Indeed, the cell phenotype influences several sequelae of GPCR activation, including GPCR oligomerization, G protein coupling, spatial organization of signaling proteins and inactivation and internalization processes. The cell phenotype, consequently, modulates both the affinity and efficacy of endogenous agonists and synthetic compounds. Emerging data suggests a complex function of GPCR signaling resulting in tissue specific responses, even those emanating from the same GPCR subtype. This short review describes some phenotypic influences on GPCR function and their implications for the use of cell-based assays used to identify and characterize GPCR ligands.
Eglen
Richard M
RM
DiscoveRx Corp, 42501 Albrae St., Fremont, CA 94538, USA. reglen@discoverx.com
D000818:Animals; D002477:Cells / Q000187:drug effects; D006801:Humans; D010641:Phenotype; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics
D043562:Receptors, G-Protein-Coupled