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Lipopolysaccharide induces alteration of serotonin transporter in human intestinal epithelial cells

Department of Pharmacology and Physiology, Faculty of Veterinary Sciences, University of Zaragoza, Zaragoza, Spain, Department of Basic Sciences, Faculty of Veterinary Sciences, University Centrooccidental Lisandro Alvarado, Estado Lara, Venezuela

Nyurky Matheus

Department of Pharmacology and Physiology, Faculty of Veterinary Sciences, University of Zaragoza, Zaragoza, Spain, Department of Basic Sciences, Faculty of Veterinary Sciences, University Centrooccidental Lisandro Alvarado, Estado Lara, Venezuela

Ruth Iceta

Department of Pharmacology and Physiology, Faculty of Veterinary Sciences, University of Zaragoza, Zaragoza, Spain

Jose E. Mesonero

Department of Pharmacology and Physiology, Faculty of Veterinary Sciences, University of Zaragoza, Zaragoza, Spain

Ana I. Alcalde

Department of Pharmacology and Physiology, Faculty of Veterinary Sciences, University of Zaragoza, Zaragoza, Spain, aalcalde{at}unizar.es

Intestinal serotoninergic activity and serotonin transporter (SERT) function have been shown to be altered in intestinal inflammatory diseases. Serotonin (5-HT) plays a critical role in the regulation of gastrointestinal physiology. Activity of 5-HT depends on its extracellular availability, partly modulated by SERT that transports 5-HT into the cell. Lipopolysaccharide (LPS) is a component of Gram-negative bacteria outer membrane, which acts as a potent activator of the inflammatory system in the intestine. The aim of this work was to determine, in the enterocyte-like cell line Caco-2, whether LPS treatment affects serotoninergic activity by acting on SERT. The results demonstrate that LPS treatment diminishes SERT activity in a dose- and period-dependent way. The kinetic study shows that V_max was significantly reduced after treatment with LPS. The LPS effect on 5-HT uptake was, in part, mediated by protein kinase C (PKC) activation. The molecular expression of SERT revealed that LPS treatment did not affect the mRNA level or the SERT protein content in cell homogenate. The level of SERT protein, however, was reduced on brush border membrane. The LPS effect might be due to an alteration of the intracellular traffic of SERT which may, in part, be mediated by PKC activity.

Key Words: Caco-2 cells • 5-HT • LPS • serotonin transporter • intestine

This version was published on August 1, 2009

Innate Immunity, Vol. 15, No. 4, 243-250 (2009)
DOI: 10.1177/1753425909104781


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