Serotonin stimulates endotoxin translocation via 5-HT3 receptors in the rat ileum.
Because few previous studies have investigated the mechanisms of endotoxin translocation induced by intestinal obstruction, we aimed to clarify whether or not serotonin [5-hydroxytryptamine (5-HT)], which is released from enterochromaffin (EC) cells, is responsible for alterations of the mucosal permeability to endotoxin and to identify the 5-HT receptor subtypes that mediate this action. FITC-labeled LPS (FITC-LPS) was injected into the ileum of rats, and the FITC-LPS level in the superior mesenteric vein was subsequently measured by using a fluorescence spectrophotometer. To measure the 5-HT release induced by high intraluminal pressure, ex vivo preparation of vascularly and luminally perfused rat ileum was used. Results demonstrated that elevated intraluminal pressure stimulates the translocation of FITC-LPS and the release of 5-HT from the EC cells into the intestinal lumen but not into the portal circulation. This FITC-LPS translocation, which was stimulated by exogenously applied 5-HT in the lumen and the jugular vein, was inhibited by 5-HT(3) receptor antagonist administration both intaluminally and intravenously. The stimulatory effect of elevated intraluminal pressure on the translocation of FITC-LPS was inhibited by the intraluminal and intravenous administration of 5-HT(3) receptor antagonist. These results suggest that 5-HT released from EC cells may be involved in the translocation of FITC-LPS induced by elevated intraluminal pressure and that this effect is mediated by 5-HT(3) receptors that may be located in the intestinal epithelium.
Yamada
Tadanori
T
Departments of Surgery and Anatomy, Shiga University of Medical Science, Seta, Otsu, Shiga 520-2192, Japan.
Inui
Akio
A
Hayashi
Naoki
N
Fujimura
Masaki
M
Fujimiya
Mineko
M
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D007082:Ileum / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism*; D008297:Male; D010539:Permeability; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013997:Time Factors
D008070:Lipopolysaccharides; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin