This Article Full Text Full Text (PDF) All Versions of this Article: 146/1/119    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Delarue, C. Articles by Vaudry, H. Search for Related Content PubMed PubMed Citation Articles by Delarue, C. Articles by Vaudry, H.

Activation of Endothelin_A Receptors in Frog Adrenocortical Cells Stimulates Both Calcium Mobilization from Intracellular Stores and Calcium Influx through L-Type Calcium Channels

European Institute for Peptide Research (Institut Fédratif de Recherches Multidisciplinaires sur les Peptides 23) (C.D., I.R.J., M.G., L.G., H.V.), Laboratory of Cellular and Molecular Neuroendocrinology (Institut National de la Santé et de la Recherche Médicale U 413), University of Rouen, 76821 Mont-Saint-Aignan, France; and Institut National de la Recherche Scientifique-Santé/Institut Armand Frappier, Université du Québec (A.F.), Pointe-Claire, Québec, Canada H9R 1G6

Address all correspondence and requests for reprints to: Dr. Hubert Vaudry, European Institute for Peptide Research (Institut Fédratif de Recherches Multidisciplinaires sur les Peptides 23), Laboratory of Cellular and Molecular Neuroendocrinology, Institut National de la Santé et de la Recherche Médicale U 413, UA Centre National de la Recherche Scientifique, University of Rouen, 76821 Mont-Saint-Aignan, France. E-mail: hubert.vaudry{at}univ-rouen.fr.

We have previously shown that endothelin (ET)-1 stimulates corticosterone and aldosterone secretion by the frog adrenal gland through activation of ET_A receptors positively coupled to both the adenylyl cyclase and phospholipase C (PLC) pathways. The purpose of the present study was to investigate the involvement of calcium in ET-1-induced stimulation of corticosteroid secretion. Cytoautoradiographic labeling using [¹²⁵I]ET-1 as a tracer revealed the presence of ET-1 binding sites on adrenocortical cells. Administration of graded concentrations of ET-1 in the vicinity of adrenocortical cells provoked a dose-dependent increase in cytosolic calcium concentrations ([Ca²⁺]_i). ET-1 induced a biphasic response consisting of an immediate and transient peak of [Ca²⁺]_i followed by a plateau phase. Preincubation of the cells with the calcium-ATPase inhibitor thapsigargin or the PLC inhibitor U-73122 reduced the amplitude of the transient phase. Administration of the calcium chelator EGTA or the protein kinase A inhibitor H-89 attenuated the plateau phase. The [Ca²⁺]_i response to ET-1 was markedly reduced during concomitant administration of U-73122 and H-89. Preincubation of the cells with the L-type calcium channel blocker nifedipine attenuated the plateau phase. Corticosteroid secretion from perifused frog adrenal slices was almost completely suppressed by thapsigargin and reduced by nifedipine. Taken together, these data indicate that activation of ET_A receptors in frog adrenocortical cells provokes immediate stimulation of PLC, which causes an early mobilization of calcium from intracellular stores, and activates adenylyl cyclase, which results in delayed calcium influx through L-type calcium channels. The resulting increase in [Ca²⁺]_i plays a pivotal role in ET-1-induced corticosteroid secretion.

This article has been cited by other articles:

				F. Zhang, G. Zhang, A. Y. Zhang, M. J. Koeberl, E. Wallander, and P.-L. Li Production of NAADP and its role in Ca2+ mobilization associated with lysosomes in coronary arterial myocytes Am J Physiol Heart Circ Physiol, July 1, 2006; 291(1): H274 - H282. [Abstract] [Full Text] [PDF]