Enhancement of ca2+ currents by ghrh, and its relation to pka and [
ob]ca2+]i in human gh-secreting adenoma cells.
Takei, Tsukasa, Koji Takano, Junko Yasufuku-Takano, Toshiro Fujita,
and Naohide Yamashita.
Fourth Department of Internal Medicine, University of Tokyo School
of Medicine, Tokyo 112, Japan
APStracts 3:0131E, 1996.
The effects of human growth hormone-releasing hormone (hGHRH) on Ca2+
channels was examined in human growth hormone-producing adenoma cells
using the perforated whole cell clamp technique. These cells
exhibited T- and L-type Ca2+ channel currents and application of 10-8
M hGHRH increased the amplitude of both currents. Application of 10-5
M 8Br-cAMP also increased T- and L-type currents. Additional
application of 10-8 M hGHRH did not further increase the current
amplitudes. Treatment with Rp-cAMPS (10-5 M) or H89 (10-5 M)
inhibited the enhancement of Ca2+ channel currents by hGHRH, as did
intracellular injection of PKI(5-24), indicating that hGHRH increased
the amplitude of Ca2+ channel currents through the activation of the
cAMP-protein kinase A (PKA) system. When intracellular Ca2+
concentration ([Ca2+]i) was chelated to less than 30 nM with
BAPTA/AM, hGHRH failed to increase the Ca2+ channel currents. In this
condition, hGHRH activated nonselective cation channels, which
revealed that the cAMP-PKA system operated after treatment with
BAPTA/AM, and that the site of low [Ca2+]i-induced inhibition of
hGHRH effects on Ca2+ channels was at a step after PKA activation.
Received 19 April 1996; accepted in final form 25 June 1996.
APS Manuscript Number E197-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996