α 2 -Adrenergic Receptors

There are three subtypes of α 2 -adrenergic receptors (α 2 -ARs), encoded by three independent, intronless genes. These subtypes are denoted as α 2A (human chromosome 10), α 2B (human chromosome 2), and α 2C (human chromosome 4). Ligand selectivity for pharmacologic agents does exist for the various α 2 -AR subtypes, although this selectivity has been observed principally in vitro because not all of these ligands have been evaluated for their pharmacokinetic properties in vivo. The lack of specific ligands for each of the α 2 -AR subtypes, particularly antagonists, has prevented the unequivocal assignment of the differing α 2 -AR subtypes to various physiologic responses. However, tools to genetically manipulate the mouse genome to create mutant or null alleles of each of these subtypes now provide an understanding of many of the roles of the different α 2 -AR subtypes. The α 2A -AR also appears to respond to endogenous catecholamines to suppress epileptogenesis (kindling) and depressive symptoms. The α 2C -AR elicits depressive behaviors, behaving functionally the opposite of the α 2A -AR subtype. The α 2B -AR, in contrast to the α 2A -AR, is involved in the vascular hypertensive effect of α 2 -AR agonists.