Deletion of the neuropeptide Y (NPY) Y1 receptor gene reveals a regulatory role of NPY on catecholamine synthesis and secretion.
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.
Cavadas
Cláudia
C
*Center for Neurosciences and Cell Biology and Faculty of Pharmacy, University of Coimbra, 3004-517 Coimbra, Portugal.
Céfai
Daniel
D
Department of Medicine, Divisions of.
Rosmaninho-Salgado
Joana
J
*Center for Neurosciences and Cell Biology and Faculty of Pharmacy, University of Coimbra, 3004-517 Coimbra, Portugal.
Vieira-Coelho
Maria Augusta
MA
Institute of Pharmacology and Therapeutics, Faculty of Medicine, 4200-319 Porto, Portugal.
Moura
Eduardo
E
Institute of Pharmacology and Therapeutics, Faculty of Medicine, 4200-319 Porto, Portugal.
Busso
Nathalie
N
Rheumatology.
Pedrazzini
Thierry
T
Department of Medicine, Divisions of.
Grand
Daniela
D
Clinical Pharmacology and Toxicology, and.
Rotman
Samuel
S
Institute of Pathology, Centre Hospitalier Universaire Vaudois, 1011 Lausanne, Switzerland; and.
Waeber
Bernard
B
**Clinical Pathophysiology, and.
Aubert
Jean-François
JF
Department of Medicine, Divisions of.
Grouzmann
Eric
E
Clinical Pharmacology and Toxicology, and eric.grouzmann@chuv.hospvd.ch.
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
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