Horm Metab Res 2017; 49(04): 269-275
DOI: 10.1055/s-0042-122781
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

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

C. Duparc
1  Normandie Univ., UNIROUEN, INSERM, U982, Laboratoire Différenciation et Communication Neuronale et Neuroendocrine, IRIB, Rouen, France
,
C. André
2  Service d’Endocrinologie, Diabète et Maladies Métaboliques, IRIB, Centre Hospitalier Universitaire – Hôpitaux de Rouen, Rouen, France
,
J. Ménard
3  Département de Biostatistiques, Centre Hospitalier Universitaire – Hôpitaux de Rouen, Rouen, France
,
B. Godouet-Getti
2  Service d’Endocrinologie, Diabète et Maladies Métaboliques, IRIB, Centre Hospitalier Universitaire – Hôpitaux de Rouen, Rouen, France
,
J. Wils
1  Normandie Univ., UNIROUEN, INSERM, U982, Laboratoire Différenciation et Communication Neuronale et Neuroendocrine, IRIB, Rouen, France
4  Laboratoire de Biochimie, Institut de Biologie Clinique, Centre Hospitalier Universitaire – Hôpitaux de Rouen, Rouen, France
,
A. F. Cailleux
2  Service d’Endocrinologie, Diabète et Maladies Métaboliques, IRIB, Centre Hospitalier Universitaire – Hôpitaux de Rouen, Rouen, France
5  CIC-CRB 1404, INSERM, Centre Hospitalier Universitaire-Hôpitaux de Rouen, Rouen, France
,
L. Moreau-Grangé
2  Service d’Endocrinologie, Diabète et Maladies Métaboliques, IRIB, Centre Hospitalier Universitaire – Hôpitaux de Rouen, Rouen, France
5  CIC-CRB 1404, INSERM, Centre Hospitalier Universitaire-Hôpitaux de Rouen, Rouen, France
,
E. Louiset
1  Normandie Univ., UNIROUEN, INSERM, U982, Laboratoire Différenciation et Communication Neuronale et Neuroendocrine, IRIB, Rouen, France
,
H. Lefebvre
1  Normandie Univ., UNIROUEN, INSERM, U982, Laboratoire Différenciation et Communication Neuronale et Neuroendocrine, IRIB, Rouen, France
2  Service d’Endocrinologie, Diabète et Maladies Métaboliques, IRIB, Centre Hospitalier Universitaire – Hôpitaux de Rouen, Rouen, France
5  CIC-CRB 1404, INSERM, Centre Hospitalier Universitaire-Hôpitaux de Rouen, Rouen, France
› Author Affiliations
Further Information

Publication History

received 29 June 2016

accepted 24 November 2016

Publication Date:
19 January 2017 (eFirst)

Abstract

In the normal human adrenal gland, serotonin (5-HT) stimulates aldosterone secretion through the 5-HT4 receptor (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-HT4 receptor 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-HT4 receptors 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-HT4 receptors.