The neuropeptide substance P regulates aldosterone secretion in human adrenals.
Adolescent
Adrenal Cortex
/ metabolism
Adrenal Glands
/ metabolism
Adult
Aldosterone
/ blood
Aprepitant
/ pharmacology
Cells, Cultured
Humans
Hypoglycemia
/ blood
Male
Metoclopramide
Mineralocorticoids
/ biosynthesis
Neurokinin-1 Receptor Antagonists
/ pharmacology
Placebos
/ administration & dosage
Proof of Concept Study
Prospective Studies
Receptors, Neurokinin-1
/ metabolism
Substance P
/ metabolism
Transaminases
/ blood
Young Adult
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
29 05 2020
29 05 2020
Historique:
received:
15
01
2019
accepted:
06
05
2020
entrez:
31
5
2020
pubmed:
31
5
2020
medline:
25
8
2020
Statut:
epublish
Résumé
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 1
Identifiants
pubmed: 32471973
doi: 10.1038/s41467-020-16470-8
pii: 10.1038/s41467-020-16470-8
pmc: PMC7260184
doi:
Substances chimiques
Mineralocorticoids
0
Neurokinin-1 Receptor Antagonists
0
Placebos
0
Receptors, Neurokinin-1
0
TACR1 protein, human
0
Aprepitant
1NF15YR6UY
Substance P
33507-63-0
Aldosterone
4964P6T9RB
Transaminases
EC 2.6.1.-
Metoclopramide
L4YEB44I46
Banques de données
ClinicalTrials.gov
['NCT00977223']
EudraCT
['2008-003367-40']
Types de publication
Clinical Trial, Phase IV
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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