Ghrh activates a nonselective cation current in human gh-secreting
adenoma cells.
Takano, Koji, Tsukasa Takei, Akira Teramoto, and Naohide Yamashita.
Fourth Department of Internal Medicine, University of Tokyo School
of Medicine, 3-28-6 Mejirodai, Bunkyo-ku, Tokyo 112, Japan,
Department of Neurosurgery, Nippon Medical School, Tokyo 112,
Japan
APStracts 3:0024E, 1996.
Electrophysiological responses induced by human growth hormone
-releasing hormone (hGHRH) were analyzed using the perforated whole
-cell clamp technique in human GH-secreting adenoma cells. Application
of hGHRH depolarized the membrane by increasing Na+ ion conductance.
The reversal potential of the hGHRH-induced current was -20 to 0 mV.
The channel was permeable to Na+, Li+ and K+, but not to TMA+. These
properties were compatible with those of nonselective cation
channels. Similar nonselective cation current was activated by 8Br
-cAMP and forskolin, and the activation of the hGHRH-induced current
was inhibited by PKA inhibitors, Rp-cAMPS and H89, and PKI(5-24),
indicating that hGHRH-induced current was activated by PKA. Cholera
toxin pretreatment eliminated the hGHRH-induced current, suggesting
that Gs is involved in the activation of this current. This current
became irreversible when the cells were pretreated with okadaic acid,
suggesting that the recovery of the hGHRH-induced current was
mediated by a serine/threonine protein phosphatase. GHRH-induced GH
secretion was inhibited in Na+-free medium, suggesting the importance
of the nonselective cation current on hGHRH-induced GH secretion. In
human GH-secreting non-adenoma cells hGHRH increased Na+ ion
conductance as was the case in GH-secreting adenoma cells.
Received 9 November 1995; accepted in final form 18 January 1996.
APS Manuscript Number E527-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 February 96