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Endocrinology Vol. 138, No. 6 2405-2409
Copyright © 1997 by The Endocrine Society

ARTICLES

Gi3 Mediates Somatostatin-Induced Activation of an Inwardly Rectifying K+ Current in Human Growth Hormone-Secreting Adenoma Cells1

Koji Takano, Junko Yasufuku-Takano, Akira Teramoto and Toshiro Fujita

Fourth Department of Internal Medicine (K.T., J.Y.-T., T.F.), University of Tokyo School of Medicine, Tokyo 112, Japan; and Department of Neurosurgery (A.T.), Nippon Medical School, Tokyo 113, Japan

Address all correspondence and requests for reprints to: Koji Takano, M.D., Ph.D., Fourth Department of Internal Medicine, University of Tokyo School of Medicine, 3–28-6 Mejirodai, Bunkyo-ku, Tokyo 112, Japan.

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.




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