title: Deletion of the neuropeptide Y (NPY) Y1 receptor gene reveals a regulatory role of NPY on catecholamine synthesis and secretion.
abstract: The contribution of neuropeptide Y (NPY), deriving from adrenal medulla, to the adrenosympathetic tone is unknown. We found that in response to NPY, primary cultures of mouse adrenal chromaffin cells secreted catecholamine, and that this effect was abolished in cultures from NPY Y(1) receptor knockout mice (Y(1)-/-). Compared with wild-type mice (Y(1)+/+), the adrenal content and constitutive release of catecholamine were increased in chromaffin cells from Y(1)-/- mice. In resting animals, catecholamine plasma concentrations were higher in Y(1)-/- mice. Comparing the adrenal glands of both genotypes, no differences were observed in the area of the medulla, cortex, and X zone. The high turnover of adrenal catecholamine in Y(1)-/- mice was explained by the enhancement of tyrosine hydroxylase (TH) activity, although no change in the affinity of the enzyme was observed. The molecular interaction between the Y(1) receptor and TH was demonstrated by the fact that NPY markedly inhibited the forskolin-induced luciferin activity in Y(1) receptor-expressing SK-N-MC cells transfected with a TH promoter sequence. We propose that NPY controls the release and synthesis of catecholamine from the adrenal medulla and consequently contributes to the sympathoadrenal tone.
authors.affiliation: *Center for Neurosciences and Cell Biology and Faculty of Pharmacy, University of Coimbra, 3004-517 Coimbra, Portugal.
authors.forename: Cláudia
authors.initials: C
authors.lastname: Cavadas
authors.affiliation: Department of Medicine, Divisions of.
authors.forename: Daniel
authors.initials: D
authors.lastname: Céfai
authors.affiliation: *Center for Neurosciences and Cell Biology and Faculty of Pharmacy, University of Coimbra, 3004-517 Coimbra, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Rosmaninho-Salgado
authors.affiliation: Institute of Pharmacology and Therapeutics, Faculty of Medicine, 4200-319 Porto, Portugal.
authors.forename: Maria Augusta
authors.initials: MA
authors.lastname: Vieira-Coelho
authors.affiliation: Institute of Pharmacology and Therapeutics, Faculty of Medicine, 4200-319 Porto, Portugal.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Moura
authors.affiliation: Rheumatology.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Busso
authors.affiliation: Department of Medicine, Divisions of.
authors.forename: Thierry
authors.initials: T
authors.lastname: Pedrazzini
authors.affiliation: Clinical Pharmacology and Toxicology, and.
authors.forename: Daniela
authors.initials: D
authors.lastname: Grand
authors.affiliation: Institute of Pathology, Centre Hospitalier Universaire Vaudois, 1011 Lausanne, Switzerland; and.
authors.forename: Samuel
authors.initials: S
authors.lastname: Rotman
authors.affiliation: **Clinical Pathophysiology, and.
authors.forename: Bernard
authors.initials: B
authors.lastname: Waeber
authors.affiliation: Department of Medicine, Divisions of.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Aubert
authors.affiliation: Clinical Pharmacology and Toxicology, and eric.grouzmann@chuv.hospvd.ch.
authors.forename: Eric
authors.initials: E
authors.lastname: Grouzmann
mesh_terms: D000311:Adrenal Glands / Q000166:cytology / Q000378:metabolism; D000818:Animals; D002395:Catecholamines / Q000096:biosynthesis* / Q000097:blood / Q000378:metabolism*; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects / Q000378:metabolism; D004837:Epinephrine / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009478:Neuropeptide Y / Q000378:metabolism* / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D017476:Receptors, Neuropeptide Y / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
chemical_list: D002395:Catecholamines; D009478:Neuropeptide Y; D012333:RNA, Messenger; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; D014446:Tyrosine 3-Monooxygenase; D009638:Norepinephrine; D004837:Epinephrine