title: Role of endothelial AADC in cardiac synthesis of serotonin and nitrates accumulation.
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.
authors: Institut National de la Santé et de la Recherche Médicale, Institut des Maladies Métaboliques et Cardiovasculaires de Rangueil, Toulouse, France.
authors: Charlotte
authors: C
authors: Rouzaud-Laborde
authors: Naïma
authors: N
authors: Hanoun
authors: Ipek
authors: I
authors: Baysal
authors: Jean-Simon
authors: JS
authors: Rech
authors: Céline
authors: C
authors: Mias
authors: Denis
authors: D
authors: Calise
authors: Pierre
authors: P
authors: Sicard
authors: Céline
authors: C
authors: Frugier
authors: Marie-Helène
authors: MH
authors: Seguelas
authors: Angelo
authors: A
authors: Parini
authors: Nathalie
authors: N
authors: Pizzinat
mesh_terms: D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism*; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D006321:Heart / Q000187:drug effects / Q000196:embryology; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000378:metabolism*; D014365:Tryptophan Hydroxylase / Q000378:metabolism
chemical_list: D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D009566:Nitrates; D012701:Serotonin; D006916:5-Hydroxytryptophan; D014365:Tryptophan Hydroxylase; D001142:Aromatic-L-Amino-Acid Decarboxylases