Dopamine induces a biphasic modulation of hypothalamic ANF neurons: a ligand concentration-dependent effect involving D-5 and D-2 receptor interaction

Increasing evidence now suggests that more than one subtype of dopamine rec eptors is co-expressed in some of the central neurons, The neurobiological effects on the host cells when these receptors are concurrently activated b y their common physiological ligand, dopamine, however, remains elusive. Am ong the members of the family of dopamine receptors, coupling of D-1-like d opamine receptors to Gs and D-2-like receptors to Gi proteins are known to augment or suppress cellular functions respectively, through modulation of adenylyl cyclase activity and consequently cAMP generation, Simultaneous ac tivation of D-1 and D-2 receptors in transfected cell lines expressing the two cloned receptors, however, produced antagonistic effects, This is in co ntrast to in vivo studies, in which concurrent activation of D-1-like and D -2-like receptors by their respective agonists may induce synergistic or an tagonistic effects or both, We report here that in long-term rat hypothalam ic cell cultures, activation of both D-1-like (D-1 and D-5) and D-2 recepto rs on atrial natriuretic factor-producing neurons by dopamine yields a biph asic response. The response is ligand concentration-dependent and involves type II adenylyl cyclases, This process is mediated primarily through antag onistic and synergistic interactions of D-5 and D-2 receptors as the event is mimicked by the concurrent activation of these two receptors co-transfec ted in CHO cells, Our present findings suggest a novel action of dopamine, and the biochemical processes involved may underlie some of the pharmacolog ical actions of atypical anti-psychotic drugs.