title: l-Lysine Acts as a Serotonin Type 4 Receptor Antagonist to Counteract In Vitro and In Vivo the Stimulatory Effect of Serotonergic Agents on Aldosterone Secretion in Man.
abstract: In the normal human adrenal gland, serotonin (5-HT) stimulates aldosterone secretion through the 5-HT4receptor (5-HT4R). However, the physiological role of the serotonergic control of adrenocortical function is not known. In the present study, we have investigated the ability of l-Lysine, which has been shown to act as a 5-HT4receptor antagonist, to counteract in vitro and in vivo the stimulatory effect of 5-HT4R agonists on aldosterone production. l-Lysine was found to inhibit aldosterone production induced by 5-HT and the 5-HT4R agonists BIMU8 from cultured human adrenocortical cells. The action of l-Lysine (4.95 g/day orally) on the adrenal cortex was also evaluated in 20 healthy volunteers in a double blind, cross-over, placebo controlled study. l-Lysine had no significant influence on basal plasma aldosterone levels and the aldosterone responses to upright posture, tetracosactide, and low sodium diet (10 mmol/day for 3 days). Conversely, l-Lysine significantly reduced the surge of plasma aldosterone induced by metoclopramide indicating that l-Lysine is able to efficiently antagonize the adrenal 5-HT4receptors in vivo. These results suggest that l-Lysine supplementation may represent a new treatment of primary adrenal diseases in which corticosteroid hypersecretion is driven by overexpressed 5-HT4receptors.
authors.affiliation: Normandie Univ., UNIROUEN, INSERM, U982, Laboratoire Différenciation et Communication Neuronale et Neuroendocrine, IRIB, Rouen, France.
authors.forename: C
authors.initials: C
authors.lastname: Duparc
authors.affiliation: Service d'Endocrinologie, Diabète et Maladies Métaboliques, IRIB, Centre Hospitalier Universitaire - Hôpitaux de Rouen, Rouen, France.
authors.forename: C
authors.initials: C
authors.lastname: André
authors.affiliation: Département de Biostatistiques, Centre Hospitalier Universitaire - Hôpitaux de Rouen, Rouen, France.
authors.forename: J
authors.initials: J
authors.lastname: Ménard
authors.affiliation: Service d'Endocrinologie, Diabète et Maladies Métaboliques, IRIB, Centre Hospitalier Universitaire - Hôpitaux de Rouen, Rouen, France.
authors.forename: B
authors.initials: B
authors.lastname: Godouet-Getti
authors.affiliation: Normandie Univ., UNIROUEN, INSERM, U982, Laboratoire Différenciation et Communication Neuronale et Neuroendocrine, IRIB, Rouen, France.
authors.forename: J
authors.initials: J
authors.lastname: Wils
authors.affiliation: Service d'Endocrinologie, Diabète et Maladies Métaboliques, IRIB, Centre Hospitalier Universitaire - Hôpitaux de Rouen, Rouen, France.
authors.forename: A F
authors.initials: AF
authors.lastname: Cailleux
authors.affiliation: Service d'Endocrinologie, Diabète et Maladies Métaboliques, IRIB, Centre Hospitalier Universitaire - Hôpitaux de Rouen, Rouen, France.
authors.forename: L
authors.initials: L
authors.lastname: Moreau-Grangé
authors.affiliation: Normandie Univ., UNIROUEN, INSERM, U982, Laboratoire Différenciation et Communication Neuronale et Neuroendocrine, IRIB, Rouen, France.
authors.forename: E
authors.initials: E
authors.lastname: Louiset
authors.affiliation: Normandie Univ., UNIROUEN, INSERM, U982, Laboratoire Différenciation et Communication Neuronale et Neuroendocrine, IRIB, Rouen, France.
authors.forename: H
authors.initials: H
authors.lastname: Lefebvre
mesh_terms: D000307:Adrenal Gland Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000311:Adrenal Glands / Q000378:metabolism* / Q000473:pathology; D000450:Aldosterone / Q000378:metabolism*; D002478:Cells, Cultured; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008239:Lysine / Q000008:administration & dosage*; D008297:Male; D044422:Receptors, Serotonin, 5-HT4 / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D058832:Serotonin 5-HT4 Receptor Antagonists / Q000008:administration & dosage*; D018490:Serotonin Agents / Q000008:administration & dosage*
chemical_list: D058832:Serotonin 5-HT4 Receptor Antagonists; D018490:Serotonin Agents; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin; D000450:Aldosterone; D008239:Lysine