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ACS Chem Neurosci. 2013 Jan 16;4(1):64-71. doi: 10.1021/cn300154j. Epub 2012 Nov 7.

Life without peripheral serotonin: insights from tryptophan hydroxylase 1 knockout mice reveal the existence of paracrine/autocrine serotonergic networks.

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Faculté de Médecine, Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8147, Hôpital Universitaire Necker - Enfants Malades, 75015, Paris, France.


Since its identification, 75 years ago, the monoamine serotonin (5-HT) has attracted considerable attention toward its role as a neurotransmitter in the central nervous system. Yet, increasing evidence, from a growing number of research groups, substantiates the fact that 5-HT regulates important nonneuronal functions. Peripheral 5-HT, synthesized by the enzyme tryptophan hydroxyase (Tph) in intestinal cells, was assumed to be distributed throughout the entire body by blood platelets and to behave as a pleiotropic hormone. A decade ago, generation of a mouse model devoid of peripheral 5-HT lead to the discovery of a second isoform of the enzyme Tph and also suggested that 5-HT might act as a local regulator in various organs. The objective of this review is to highlight the newly discovered functions played by the monoamine using the Tph1 KO murine model and to outline current findings that led to the discovery of complete serotonergic systems in unexpected organs. Within an organ, both the presence of local Tph enzymatic activity and serotonergic components are of particular importance as they support the view that 5-HT meets the criteria to be qualified as a monoamine with a paracrine/autocrine function.

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