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Ligand-Induced 5-HT3 Receptor Internalization in Enteric Neurons in Rat Ileum

Freeman, Samara L. ; Glatzle, Jorg ; Robin, Carla S. ; Valdellon, Melissa ; Sternini, Catia ; Sharp, James W. ; Raybould, Helen E.

Gastroenterology (New York, N.Y. 1943), 2006-07, Vol.131 (1), p.97-107 [Periódico revisado por pares]

United States: Elsevier Inc

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Título:
Ligand-Induced 5-HT3 Receptor Internalization in Enteric Neurons in Rat Ileum
Autor: Freeman, Samara L. ; Glatzle, Jorg ; Robin, Carla S. ; Valdellon, Melissa ; Sternini, Catia ; Sharp, James W. ; Raybould, Helen E.
Assuntos: Animals ; Blotting, Western ; Fluoxetine - pharmacology ; Ileum - innervation ; Ileum - metabolism ; Immunohistochemistry ; Intestinal Absorption - drug effects ; Intestinal Absorption - physiology ; Intestinal Mucosa - drug effects ; Intestinal Mucosa - innervation ; Intestinal Mucosa - metabolism ; Male ; Myenteric Plexus - drug effects ; Myenteric Plexus - metabolism ; Neurons - drug effects ; Neurons - metabolism ; Ondansetron - pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Serotonin, 5-HT3 - drug effects ; Receptors, Serotonin, 5-HT3 - metabolism ; Serotonin Antagonists - pharmacology ; Serotonin Uptake Inhibitors - pharmacology
É parte de: Gastroenterology (New York, N.Y. 1943), 2006-07, Vol.131 (1), p.97-107
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Descrição: Background & Aims: Release of 5-hydroxytryptamine (5-HT) from mucosal enterochromaffin cells and activation of 5-HT3 receptors (5-HT3Rs) on neurons in the gut wall is important in the response of the gut to the luminal environment. Intestinal inflammation is associated with increased levels of mucosal 5-HT. The aims of the study were to determine the following: (1) if 5-HT3R undergoes ligand-induced internalization in myenteric neurons, and (2) the effect of long-term increase of mucosal 5-HT on 5-HT3Rs. Methods: Acute effects of exogenous 5-HT or endogenous release of 5-HT by luminal glucose on cellular localization of 5-HT3Rs was determined by immunohistochemistry and confocal microscopy. Treatment with the serotonin re-uptake inhibitor, fluoxetine, for 6 days (20 mg/kg daily orally) was used to increase mucosal 5-HT chronically in rats. Net ileal fluid movement was measured in anesthetized rats by the weight change of a 2.5% agarose cylinder. Results: Acute increases in 5-HT induced by exogenous or endogenous 5-HT decreased 5-HT3R immunoreactivity at the neuronal cell membrane by 70% and 60%, respectively. Chronic fluoxetine treatment increased mucosal levels of 5-HT and decreased membrane 5-HT3R immunoreactivity by 27%. Net fluid absorption was decreased by a 5-HT3R agonist or by luminal glucose; this was attenuated 88% and 99%, respectively, by fluoxetine treatment. Conclusions: Long-term increase in 5-HT in the intestinal mucosa results in increased 5-HT3R internalization in myenteric neurons. Chronic changes in mucosal 5-HT may alter gastrointestinal secretory and motor function via ongoing loss of receptor from neuronal membrane, causing a mismatch between luminal content and absorption.
Editor: United States: Elsevier Inc
Idioma: Inglês

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Ligand-Induced 5-HT3 Receptor Internalization in Enteric Neurons in Rat Ileum

Freeman, Samara L. ; Glatzle, Jorg ; Robin, Carla S. ; Valdellon, Melissa ; Sternini, Catia ; Sharp, James W. ; Raybould, Helen E.

United States: Elsevier Inc

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