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Role of endothelial AADC in cardiac synthesis of serotonin and nitrates accumulation.
Rouzaud-Laborde C., Hanoun N., Baysal I., Rech J.-S., Mias C., Calise D., Sicard P., Frugier C., Seguelas M.-H., Parini A. et al
PLoS ONE 7, 7 (2012) e34893 - http://www.hal.inserm.fr/inserm-00756470
Role of endothelial AADC in cardiac synthesis of serotonin and nitrates accumulation.
Charlotte Rouzaud-Laborde1, 2, Naïma Hanoun3, 4, Ipek Baysal2, Jean-Simon Rech2, Céline Mias2, Denis Calise2, Pierre Sicard2, Céline Frugier2, Marie-Helène Seguelas2, Angelo Parini1, 2, Nathalie Pizzinat2
1 :  Pôle Pharmacie
CHU Toulouse
1 av Prof Jean Poulhès TSA 50032 31059 Toulouse cedex 9
2 :  I2MC - Institut des Maladies Métaboliques et Cardiovasculaires
INSERM : U1048 – Université Paul Sabatier (UPS) - Toulouse III – Hôpital de Rangueil
1 avenue du Prof Jean Poulhes - BP 84225 - 31432 Toulouse Cedex 4
3 :  Goethe University
Goethe University
Senckenberganlage 31 60325 Frankfurt am Main
4 :  CRCT - Centre de Recherche en Cancérologie de Toulouse
INSERM : U1037 – Hôpital Purpan – CHU Toulouse
Place du Docteur Baylac - BP 3028 - 31024 Toulouse Cedex 3
Serotonin (5-HT) regulates different cardiac functions by acting directly on cardiomyocytes, fibroblasts and endothelial cells. Today, it is widely accepted that activated platelets represent a major source of 5-HT. In contrast, a supposed production of 5-HT in the heart is still controversial. To address this issue, we investigated the expression and localization of 5-HT synthesizing enzyme tryptophan hydroxylase (TPH) and L-aromatic amino acid decarboxylase (AADC) in the heart. We also evaluated their involvement in cardiac production of 5-HT. TPH1 was weakly expressed in mouse and rat heart and appeared restricted to mast cells. Degranulation of mast cells by compound 48/80 did not modify 5-HT cardiac content in mice. Western blots and immunolabelling experiments showed an abundant expression of AADC in the mouse and rat heart and its co-localization with endothelial cells. Incubation of cardiac homogenate with the AADC substrate (5-hydroxy-L-tryptophan) 5-HTP or intraperitoneal injection of 5-HTP in mice significantly increased cardiac 5-HT. These effects were prevented by the AADC inhibitor benserazide. Finally, 5-HTP administration in mice increased phosphorylation of aortic nitric oxide synthase 3 at Ser (1177) as well as accumulation of nitrates in cardiac tissue. This suggests that the increase in 5-HT production by AADC leads to activation of endothelial and cardiac nitric oxide pathway. These data show that endothelial AADC plays an important role in cardiac synthesis of 5-HT and possibly in 5-HT-dependent regulation of nitric oxide generation.

Articles dans des revues avec comité de lecture
Publisher Public Library of Science
ISSN 1932-6203