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 receptor subtypes (D-1 and D-5) couple to the G protein G(s) and activate adenylyl cyclase. The other receptor subtypes belong to the D-2-like subfamily (D-2, D-3, and D-4) and are prototypic of G protein-coupled receptors that inhibit adenylyl cyclase and activate K+ channels. The genes for the D-1 and D-5 receptors a-e intronless, but pseudogenes of the D-5 exist. The D-2 and D-3 receptors vary in Certain tissues and species 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 involved in the control of locomotion, cognition, emotion, and affect as well as neuroendocrine secretion. Ln the periphery, dopamine receptors are present more prominently in kidney, vasculature, and pituitary, where they affect mainly sodium homeostasis, vascular tone, and hormone secretion. Numerous genetic linkage analysis studies have failed so far to reveal unequivocal evidence for the involvement of one of these receptors in the etiology of various central nervous system disorders. However, targeted deletion of several of these dopamine receptor genes in mice should provide valuable information about their physiological functions.