title: Characterization of serotonin(4) receptors in adrenocortical aldosterone-producing adenomas: in vivo and in vitro studies.
abstract: We have previously shown that serotonin (5-HT) stimulates aldosterone secretion from the human adrenal gland through activation of 5-HT(4) receptors. The aim of the present study was to investigate in vivo and in vitro the presence of 5-HT(4) 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-HT(4) ligands on aldosterone production from aldosteronoma tissues were studied in vitro using a perifusion system technique. 5-HT and the 5-HT(4) 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-HT(4) receptor antagonist GR 113808 (10(-7) M, 150 min). PCR amplification revealed the expression of 5-HT(4) receptor mRNA in 13 of 14 aldosteronomas studied. Taken together, these data show that most aldosteronomas, like normal glomerulosa cells, express a functional 5-HT(4) 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.
authors.affiliation: European Institute for Peptide Research (IFRMP 23), Department of Endocrinology, INSERM, U-413, Centre Hospitalo-Universitaire de Rouen, 76031 Rouen, France. herve.lefebvre@chu-rouen.fr
authors.forename: Herve
authors.initials: H
authors.lastname: Lefebvre
authors.forename: Dorthe
authors.initials: D
authors.lastname: Cartier
authors.forename: Celine
authors.initials: C
authors.lastname: Duparc
authors.forename: Isabelle
authors.initials: I
authors.lastname: Lihrmann
authors.forename: Vincent
authors.initials: V
authors.lastname: Contesse
authors.forename: Catherine
authors.initials: C
authors.lastname: Delarue
authors.forename: Michel
authors.initials: M
authors.lastname: Godin
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Fischmeister
authors.forename: Hubert
authors.initials: H
authors.lastname: Vaudry
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Kuhn
mesh_terms: D000236:Adenoma / Q000378:metabolism*; D000306:Adrenal Cortex Neoplasms / Q000378:metabolism*; D000328:Adult; D000450:Aldosterone / Q000096:biosynthesis*; D020117:Cisapride / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011985:Receptors, Serotonin / Q000378:metabolism*; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin / Q000494:pharmacology; D018490:Serotonin Agents / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D007211:Indoles; D011985:Receptors, Serotonin; D018490:Serotonin Agents; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013449:Sulfonamides; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin; D000450:Aldosterone; D020117:Cisapride; C082871:GR 113808