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AJP - Endocrinology and Metabolism, Vol 271, Issue 5 E801-E807, Copyright © 1996 by American Physiological Society
ARTICLES |
T. Takei, K. Takano, J. Yasufuku-Takano, T. Fujita and N. Yamashita
Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Japan.
The effects of human growth hormone-releasing hormone (hGHRH) on Ca2+ channels were 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 8-bromoadenosine 3',5'-cyclic monophosphate also increased T- and L-type currents. Additional application of 10(-8) M hGHRH did not further increase the current amplitudes. Treatment with the Rp diastereomer of adenosine 3',5'-cyclic monophosphothioate (10(-5) M) or H-89 (10(-5) M) inhibited the enhancement of Ca2+ channel currents by hGHRH, as did intracellular injection of protein kinase A (PKA) inhibitor peptide [PKI-(5-24)], indicating that hGHRH increased the amplitude of Ca2+ channel currents through the activation of the adenosine 3',5'-cyclic monophosphate (cAMP)-PKA system. When intracellular Ca2+ concentration ([Ca2+]i) was chelated to < 30 nM with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTAAM), 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.
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T. Takei, J. Yasufuku-Takano, K. Takano, T. Fujita, and N. Yamashita Effect of Ca2+ and cAMP on capacitance-measured hormone secretion in human GH-secreting adenoma cells Am J Physiol Endocrinol Metab, October 1, 1998; 275(4): E649 - E654. [Abstract] [Full Text] [PDF] |
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