Classification of Adrenergic Receptor Subtypes: Molecular Biologic Approaches

Adrenergic receptors have been studied extensively for more than 30 years, first by physiological means, later with pharmacologic and biochemical approaches, and within the past several years by molecular biology. This extensive body of work provided the basis for subdividing the adrenergic receptors into β-, α₁-, and α₂-adrenergic receptor types and, subsequently, into β₁-, β₂-, α_1A-, α_1B-, α_2A-, and α_2B-adrenergic receptor subtypes. Although the pharmacologic approach indicated that there exist multiple subtypes of each type of adrenergic receptor, it was the molecular cloning of adrenergic receptor cDNAs/genes that demonstrated the existence of three genes encoding each adrenergic receptor type in humans and rats (and therefore probably in all mammals). The nine adrenergic receptor proteins expressed in cultured cells faithfully mimic the basic pharmacologic and biochemical properties ascribed to these receptors. In this article, we review the molecular cloning and characterization of the adrenergic receptors with special emphasis on the α₂-adrenergic receptors and we discuss a classification scheme based on the hypothetical molecular evolution of the adrenergic receptors.