Adrenergic Receptors as Models for G Protein-Coupled Receptors

Abstract

Approximately 80% of known hormones and neurotransmitters activate cellular signal transduction mechanisms by activating G protein-coupled receptors (Birnbaumer et al 1990). Studying the structure and function of these receptors has been challenging because they are not naturally abun­ dant proteins and they require a lipid environment to be fully active. The eDNA or genomic clones for many members of this class of receptors have recently been obtained. Applying the techniques of molecular biology to the study of G protein-coupled receptors has helped circumvent many of the technical difficulties that had complicated previous efforts to charac­ terize these proteins biochemically. The adrenergic receptors have been one of the most extensively studied classes of G protein-coupled receptors. Genomic and/or cDNA clones for nine types of adrenergic receptors have been obtained: two types of (XI receptors (Cotecchia et al 1988; Schwinn et al 1990); three types of C(2 receptors (Kobilka et al 1987; Lomasney et al 1990; Regan et al 1988; Weinshank et aI 1990); the /31 receptor (Frielle et aI 19 87); the /32 receptor (Dixon et al 1986); the /3 3 receptor (Emorine et al 1989) ; and the avian /3 receptor (Yarden et al 1986). Significant progress has been made in eluci­ dating the structural domains involved in ligand binding, G protein acti­ vation, and desensitization, and much of what is learned about the mech­ anism of action of adrenergic receptors will likely apply to the other