Gi3 mediates somatostatin-induced activation of an inwardly rectifying K+ current in human growth hormone-secreting adenoma cells.
SRIF activates an inwardly rectifying K+ current in human GH-secreting adenoma cells. Activation of this K+ current induces hyperpolarization of the membrane and abolishment of action potential firing. This mechanism is an essential mechanism for SRIF-induced decrease in intracellular Ca2+ concentration and inhibition of GH secretion. The activation of the inwardly rectifying K+ current is mediated by a pertussis toxin-sensitive G protein. In this article, the expression of the pertussis toxin-sensitive G protein alpha-subunits in the human GH-secreting adenoma cells were analyzed by RT-PCR, and the G protein transducing the SRIF-induced activation of this inwardly rectifying K+ current was investigated. RT-PCR of the messenger RNA from two human GH-secreting adenomas revealed that all G alpha(i1), G alpha(i2), G alpha(i3), and G alpha(o) were expressed in these adenomas. Primary cultured cells from these two adenoma cells were investigated under the voltage clamp of the whole-cell mode. Specific antibodies against the carboxyl terminus of G protein alpha-subunits were microinjected into the cells. Microinjection of antibody against the carboxyl terminal sequence of G alpha(i3) attenuated the SRIF-induced activation of the inwardly rectifying K+ current, whereas antibody against the common carboxyl terminal sequence of G alpha(i1) and G alpha(i2) did not. These data indicate that the G protein transducing the SRIF-induced activation of the inwardly rectifying K+ current is Gi3.
Takano
K
K
Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Bunkyo-ku, Japan.
Yasufuku-Takano
J
J
Teramoto
A
A
Fujita
T
T
D000236:Adenoma / Q000378:metabolism / Q000503:physiopathology*; D017931:DNA Primers; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000502:physiology*; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin; D010911:Pituitary Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D016133:Polymerase Chain Reaction; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger / Q000096:biosynthesis; D013004:Somatostatin / Q000494:pharmacology*; D014158:Transcription, Genetic; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D017931:DNA Primers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; D010566:Virulence Factors, Bordetella; D019382:Human Growth Hormone; D013004:Somatostatin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins