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 Ca(2+)-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 D2-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 microM) evoked a spontaneous increase in the K+ 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 microM) 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Takano
K
K
Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Japan.
Asano
S
S
Yamashita
N
N
D004298:Dopamine / Q000494:pharmacology*; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D013006:Growth Hormone / Q000096:biosynthesis*; D006801:Humans; D011188:Potassium / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism*; D013004:Somatostatin / Q000494:pharmacology; D013469:Sulpiride / Q000494:pharmacology
D015221:Potassium Channels; D013004:Somatostatin; D013469:Sulpiride; D013006:Growth Hormone; D019204:GTP-Binding Proteins; D011188:Potassium; D004298:Dopamine