DOPAMINE-RECEPTORS - FROM STRUCTURE TO FUNCTION

The diverse physiological actions of dopamine are mediated by at least live distinct G protein-coupled receptor subtypes. Two D-1-like recep tor subtypes (D-1 and D-5) couple to the G protein G(s) and activate a denylyl cyclase. The other receptor subtypes belong to the D-2-like su bfamily (D-2, D-3, and D-4) and are prototypic of G protein-coupled re ceptors that inhibit adenylyl cyclase and activate K+ channels. The ge nes for the D-1 and D-5 receptors a-e intronless, but pseudogenes of t he D-5 exist. The D-2 and D-3 receptors vary in Certain tissues and sp ecies as a result of alternative splicing, and the human D-4 receptor gene exhibits extensive polymorphic variation. Ln the central nervous system, dopamine receptors are widely expressed because they are invol ved in the control of locomotion, cognition, emotion, and affect as we ll as neuroendocrine secretion. Ln the periphery, dopamine receptors a re present more prominently in kidney, vasculature, and pituitary, whe re they affect mainly sodium homeostasis, vascular tone, and hormone s ecretion. Numerous genetic linkage analysis studies have failed so far to reveal unequivocal evidence for the involvement of one of these re ceptors in the etiology of various central nervous system disorders. H owever, targeted deletion of several of these dopamine receptor genes in mice should provide valuable information about their physiological functions.