ACTIVATION OF G-PROTEIN-COUPLED K+ CHANNELS BY DOPAMINE IN HUMAN GH-PRODUCING CELLS

Dopamine (DA) inhibited the secretion of growth hormone (GH) from cultured human GH-secreting adenoma cells. The mechanism of this DA effect on these cultured cells was investigated with electrophysiological techniques. Under current clamp, DA (10(-6) M) hyperpolarized the membrane and arrested Ca2+-dependent action potentials. Voltage clamp experiments revealed that this membrane hyperpolarization was the result of a K+ conductance increase caused by DA. The current-voltage relationship of the DA-induced K+ current showed an inward-going rectification. Application of sulpiride (10(-6) M) abolished the DA-induced K+ current, indicating that the hyperpolarization was caused by the activation of D-2-like receptors. Pertussis toxin (PTX) treatment eliminated the DA-induced K+ current as well as the DA-induced inhibition of GH secretion. An intracellular application of guanosine-5'-O-(3-thiotriphosphate) (100 mu M) evoked a spontaneous increase in the Ki current in the absence of an agonist, and the application of DA did not further increase conductance. Intracellular application of guanosine-5'-O-(2-thiodiphosphate) (2 mM) inhibited the DA-induced K+ current. These results indicate that the DA-induced K+ channel is coupled to a G protein. When adenosine 3',5'-cyclic monophosphate (cAMP, 100 mu M) was added to the patch-pipette solution, the DA-induced K+ current was still observed, indicating that the DA-induced K+ current was not caused by an inhibition of cAMP production. Somatostatin (SRIF), which also activates an inwardly rectifying K+ current through a PTX-sensitive mechanism, did not exert an additive effect on the DA-induced K+ current, indicating that the SRIF effect and the DA effect converge on the same K+ channel.