AJP - Endocrinology and Metabolism, Vol 270, Issue 6 E1050-E1057, Copyright © 1996 by American Physiological Society
GHRH activates a nonselective cation current in human GH-secreting adenoma cells
K. Takano, T. Takei, A. Teramoto and N. Yamashita
Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Japan.
Electrophysiological responses induced by human (h) growth
hormone-releasing hormone (GHRH) were analyzed using the perforated whole
cell clamp technique in human growth hormone (GH)-secreting adenoma cells.
Application of hGHRH depolarized the membrane by increasing Na+
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 8-bromoadenosine
3',5'-cyclic monophosphate and forskolin, and the activation of the
hGHRH-induced current was inhibited by protein kinase A (PKA) inhibitors,
(R)-p-adenosine 3',5'-cyclic monophosphate and
N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoleinsulfonamide, and PKA
inhibitor peptide 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 nonadenoma cells, hGHRH increased Na+ conductance, as was the
case in GH-secreting adenoma cells.
