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

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


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Soumis le : vendredi 23 novembre 2012 - 10:00:02
Dernière modification le : vendredi 23 novembre 2012 - 10:00:02

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Charlotte Rouzaud-Laborde, Naïma Hanoun, Ipek Baysal, Jean-Simon Rech, Céline Mias, et al.. Role of endothelial AADC in cardiac synthesis of serotonin and nitrates accumulation.. PLoS ONE, Public Library of Science, 2012, 7 (7), pp.e34893. <10.1371/journal.pone.0034893>. <inserm-00756470>

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