D-2, D-3, AND D-4 DOPAMINE-RECEPTORS COUPLE TO G-PROTEIN-REGULATED POTASSIUM CHANNELS IN XENOPUS OOCYTES

Human D-2, D-3, D-4 and dopamine receptors were individually coexpress ed in Xenopus oocytes with a G protein-regulated inwardly rectifying p otassium channel (GIRK1). At - 100 mV in 96 mM potassium, dopamine (0. 1-100 nM) evoked an inward current; the current showed inward rectific ation, reversed polarity at 0 mV, and was blocked by barium (50% inhib ition by 10 mu M). The concentrations of dopamine activating 50% of th e maximal current (EC(50)) were not different (2-4 nM) for D-2, D-3, a nd D-4 receptors, but the maximal current was 3-fold larger for D-2 an d D-4 than for D-3 receptors. Dopamine evoked reproducible inward curr ents at D-2 and D-4 receptors when applied repeatedly, but second resp onses could not be observed in oocytes expressing D-3 receptors. 7-Hyd roxy-N,N-di-n-propyl-2-aminotetralin mimicked the effect of dopamine ( EC(50) of similar to 2, similar to 3, and similar to 19 nM at D-2, D-3 , and D-4, respectively). (-)-Sulpiride reversibly blocked the dopamin e-induced current with IC50 values of 5, 300, and 2000 nM for D-2, D-3 , and D-4 receptors, respectively. Dopamine was ineffective in oocytes injected 2 hr previously with pertussis toxin. We concluded that all three D-2-like dopamine receptors share the potential to activate inwa rdly rectifying potassium channels.