This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted 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 Lefebvre, H. Articles by Kuhn, J.-M. Search for Related Content PubMed PubMed Citation Articles by Lefebvre, H. Articles by Kuhn, J.-M.

Characterization of Serotonin₄ Receptors in Adrenocortical Aldosterone-Producing Adenomas: In Vivo and in Vitro Studies

European Institute for Peptide Research (IFRMP 23), Department of Endocrinology, INSERM, U-413 (H.L., J.M.K.), and Department of Nephrology (M.G.), Centre Hospitalo-Universitaire de Rouen, 76031 Rouen, France; Laboratory of Cellular and Molecular Neuroendocrinology, INSERM, U-413, UA Centre National de la Recherche Scientifique, University of Rouen (H.L., D.C., C.Du., I.L., V.C., C.De., H.V., J.M.K.), 76821 Mont Saint Aignan, France; and Laboratory of Cellular and Molecular Cardiology, INSERM, U-446, Faculty of Pharmacy, University Paris-Sud (R.F.), 92296 Chatenay-Malabry, France

Address all correspondence and requests for reprints to: Dr. Hervé Lefebvre, IFRMP 23, Department of Endocrinology, INSERM, U-413, Hospital of Boisguillaume, Centre Hospitalo-Universitaire de Rouen, 76031 Rouen Cedex, France. E-mail: . herve.lefebvre{at}chu-rouen.fr

Abstract

We have previously shown that serotonin (5-HT) stimulates aldosterone secretion from the human adrenal gland through activation of 5-HT₄ receptors. The aim of the present study was to investigate in vivo and in vitro the presence of 5-HT₄ receptors in aldosterone-producing adenomas (aldosteronomas). Eight patients with aldosteronoma received a single oral dose of placebo or cisapride (10 mg). Cisapride administration significantly increased plasma aldosterone within 120 min without any significant change in renin, cortisol, or potassium levels. In two patients, a marked decrease in the plasma aldosterone response to cisapride was observed after surgical removal of the tumor. The effects of 5-HT and selective 5-HT₄ ligands on aldosterone production from aldosteronoma tissues were studied in vitro using a perifusion system technique. 5-HT and the 5-HT₄ receptor agonist cisapride (10^-7 M, 20 min) both stimulated aldosterone secretion from aldosteronoma slices. The 5-HT- and cisapride-evoked aldosterone responses were inhibited by concomitant administration of the specific 5-HT₄ receptor antagonist GR 113808 (10^-7 M, 150 min). PCR amplification revealed the expression of 5-HT₄ receptor mRNA in 13 of 14 aldosteronomas studied. Taken together, these data show that most aldosteronomas, like normal glomerulosa cells, express a functional 5-HT₄ receptor. Our results also suggest that 5-HT, which can be locally released by intratumoral mast cells, may play a role in the pathophysiology of these tumors.

This article has been cited by other articles:

				A. Lampron, I. Bourdeau, S. Oble, A. Godbout, W. Schurch, P. Arjane, P. Hamet, and A. Lacroix Regulation of Aldosterone Secretion by Several Aberrant Receptors Including for Glucose-Dependent Insulinotropic Peptide in a Patient with an Aldosteronoma J. Clin. Endocrinol. Metab., March 1, 2009; 94(3): 750 - 756. [Abstract] [Full Text] [PDF]

				O Zwermann, Y Suttmann, M Bidlingmaier, F Beuschlein, and M Reincke Screening for membrane hormone receptor expression in primary aldosteronism Eur. J. Endocrinol., March 1, 2009; 160(3): 443 - 451. [Abstract] [Full Text] [PDF]

				P. Ye, B. Mariniello, F. Mantero, H. Shibata, and W. E Rainey G-protein-coupled receptors in aldosterone-producing adenomas: a potential cause of hyperaldosteronism J. Endocrinol., October 1, 2007; 195(1): 39 - 48. [Abstract] [Full Text] [PDF]

				D. Cartier, S. Jegou, F. Parmentier, I. Lihrmann, E. Louiset, J.-M. Kuhn, C. Bastard, P.-F. Plouin, M. Godin, H. Vaudry, et al. Expression profile of serotonin4 (5-HT4) receptors in adrenocortical aldosterone-producing adenomas Eur. J. Endocrinol., December 1, 2005; 153(6): 939 - 947. [Abstract] [Full Text] [PDF]

				V. Contesse, Y. Reznik, E. Louiset, C. Duparc, D. Cartier, F. Sicard, A. Laquerriere, F. Parmentier, J.-M. Kuhn, H. Vaudry, et al. Abnormal Sensitivity of Cortisol-Producing Adrenocortical Adenomas to Serotonin: In Vivo and in Vitro Studies J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2843 - 2850. [Abstract] [Full Text] [PDF]

				M. Mannelli, P. Ferruzzi, P. Luciani, C. Crescioli, L. Buci, G. Corona, M. Serio, and A. Peri Cushing's Syndrome in a Patient with Bilateral Macronodular Adrenal Hyperplasia Responding to Cisapride: An in Vivo and in Vitro Study J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4616 - 4622. [Abstract] [Full Text] [PDF]