Localization and trafficking of alpha(2)-adrenergic receptor subtypes in cells and tissues

The three alpha(2)-adrenergic receptor (alpha(2)AR) subtypes, all of which couple to multiple effecters via G(i)/G(o), proteins, perform various funct ions, including the mediation of decreases in adenylyl cyclase activity, ac tivation of receptor-mediated K+ channels, and inhibition of voltage-gated Ca2+ channels. The alpha(2)ARs are polarized in many target cells, such as neurons in the peripheral and central nervous system and in intestinal and renal epithelia. Precise targeting and polarization of molecules are crucia l for many physiological processes, and may confer a degree of specificity that, in the case of the adrenergic receptors, could represent a reasonable strategy by which catecholamines coordinate cellular function in a highly specific way. Receptors also redistribute in response to agonist occupancy by means of sequestration, endocytosis, recycling, or, alternatively, down- regulation (degradation). The focus of this review is to compare the simila rities and differences among the three alpha(2)AR subtypes in terms of spec ificity, signaling, and trafficking. It is anticipated that a molecular und erstanding of receptor trafficking will lead to novel therapeutic strategie s for diseases linked to aberrant adrenergic receptor function or localizat ion. (C) 1999 Elsevier Science Inc. All rights reserved.