Role of endothelial AADC in cardiac synthesis of serotonin and nitrates accumulation.

Charlotte Rouzaud-Laborde; Naïma Hanoun; Ipek Baysal; Jean-Simon Rech; Céline Mias; Denis Calise; Pierre Sicard; Céline Frugier; Marie-Helène Seguelas; Angelo Parini; Nathalie Pizzinat

doi:10.1371/journal.pone.0034893

Role of endothelial AADC in cardiac synthesis of serotonin and nitrates accumulation.

Charlotte Rouzaud-Laborde ^{1, 2} Naïma Hanoun ^{3, 4} Ipek Baysal ² Jean-Simon Rech ² Céline Mias ² Denis Calise ² Pierre Sicard ² Céline Frugier ² Marie-Helène Seguelas ² Angelo Parini ^{1, 2} Nathalie Pizzinat ²

1 Pôle Pharmacie

2 I2MC - Institut des Maladies Métaboliques et Cardiovasculaires

3 Goethe University

4 CRCT - Centre de Recherche en Cancérologie de Toulouse

Abstract : 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.

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Article dans une revue

PLoS ONE, Public Library of Science, 2012, 7 (7), pp.e34893. <10.1371/journal.pone.0034893>

http://www.hal.inserm.fr/inserm-00756470
Contributeur : Marie Francoise Simon <>
Soumis le : vendredi 23 novembre 2012 - 10:02:31
Dernière modification le : vendredi 23 novembre 2012 - 11:43:10

Role of endothelial AADC in cardiac synthesis of serotonin and nitrates accumulation.

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