The neuropeptide substance P regulates aldosterone secretion in human adrenals

Autor: Saloua Cherifi, Guillaume Defortescu, Julien Wils, Estelle Louiset, Françoise Gobet, C. Guiheneuf, Céline Duparc, Antoine-Guy Lopez, Christophe Dubessy, Anne Cailleux, Hadrien-Gaël Boyer, Bruno Cauliez, Hervé Lefebvre, J.F. Ménard, Isabelle Boutelet
Přispěvatelé: CHU Rouen, Normandie Université (NU), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'endocrinologie, diabétologie et maladies métaboliques [Rouen], Laboratoire de biochimie générale [Rouen], Normandie Université (NU)-Centre hospitalier universitaire de Rouen, Service d'urologie [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), DUPARC, Céline, Hôpital Charles Nicolle [Rouen], Université Le Havre Normandie (ULH), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Adult
Male
medicine.medical_specialty
Adolescent
Metoclopramide
Physiology
Science
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Neuropeptide
Substance P
Proof of Concept Study
Article
Placebos
Young Adult
chemistry.chemical_compound
Endocrinology
Neurokinin-1 Receptor Antagonists
Mineralocorticoids
Internal medicine
Adrenal Glands
Renin–angiotensin system
Humans
Medicine
Prospective Studies
lcsh:Science
Receptor
Aldosterone
Cells
Cultured
Transaminases
Aprepitant
[SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
business.industry
[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Receptors
Neurokinin-1
[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
Hypoglycemia
3. Good health
Autonomic nervous system
chemistry
Adrenal Cortex
lcsh:Q
business
Homeostasis
medicine.drug
Zdroj: Nature Communications
Nature Communications, Nature Publishing Group, 2020, 11 (1), pp.2673. ⟨10.1038/s41467-020-16470-8⟩
Nature Communications, Vol 11, Iss 1, Pp 1-11 (2020)
Nature Communications, 2020, 11 (1), pp.2673. ⟨10.1038/s41467-020-16470-8⟩
ISSN: 2041-1723
Popis: Aldosterone, produced by the adrenals and under the control of plasma angiotensin and potassium levels, regulates hydromineral homeostasis and blood pressure. Here we report that the neuropeptide substance P (SP) released by intraadrenal nerve fibres, stimulates aldosterone secretion via binding to neurokinin type 1 receptors (NK1R) expressed by aldosterone-producing adrenocortical cells. The action of SP is mediated by the extracellular signal-regulated kinase pathway and involves upregulation of steroidogenic enzymes. We also conducted a prospective proof-of-concept, double blind, placebo-controlled clinical trial aimed to investigate the impact of the NK1R antagonist aprepitant on aldosterone secretion in healthy male volunteers (EudraCT: 2008-003367-40, ClinicalTrial.gov: NCT00977223). Participants received during two 7-day treatment periods aprepitant (125 mg on the 1st day and 80 mg during the following days) or placebo in a random order at a 2-week interval. The primary endpoint was plasma aldosterone levels during posture test. Secondary endpoints included basal aldosterone alterations, plasma aldosterone variation during metoclopramide and hypoglycaemia tests, and basal and stimulated alterations of renin, cortisol and ACTH during the three different stimulatory tests. The safety of the treatment was assessed on the basis of serum transaminase measurements on days 4 and 7. All pre-specified endpoints were achieved. Aprepitant decreases aldosterone production by around 30% but does not influence the aldosterone response to upright posture. These results indicate that the autonomic nervous system exerts a direct stimulatory tone on mineralocorticoid synthesis through SP, and thus plays a role in the maintenance of hydromineral homeostasis. This regulatory mechanism may be involved in aldosterone excess syndromes.
Adrenal aldosterone production is regulated by plasma angiotensin and potassium levels. Here the authors report that the neuropeptide substance P stimulates aldosterone production via neurokinin type 1 receptors (NK1R), and report a proof-of-concept placebo controlled clinical trial showing that a NK1R antagonist decreases aldosterone levels.
Databáze: OpenAIRE
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