G-PROTEIN-COUPLED RECEPTORS - FUNCTIONAL AND MECHANISTIC INSIGHTS THROUGH ALTERED GENE-EXPRESSION

G protein-coupled receptors (GPCRs) comprise a large and diverse famil y of molecules that play essential roles in signal transduction. In ad dition to a constantly expanding pharmacological repertoire, recent ad vances in the ability to manipulate GPCR expression in vivo have provi ded another valuable approach in the study of GPCR function and mechan ism of action. Current technologies now allow investigators to manipul ate GPCR expression in a variety of ways. Graded reductions in GPCR ex pression can be achieved through antisense strategies or total gene ab lation or replacement can be achieved through gene targeting strategie s, and exogenous expression of wild-type or mutant GPCR isoforms can b e accomplished with transgenic technologies. Both the techniques used to achieve these specific alterations and the consequences of altered expression patterns are reviewed here and discussed in the context of GPCR function and mechanism of action.