Inhibition of 5-hydroxytryptamine- and enterotoxin-induced fluid secretion by 5-HT receptor antagonists in the rat jejunum.
The effects of cholera toxin and heat stable Escherichia coli (E. coli) enterotoxin on intestinal fluid secretion are commonly considered to be mediated by cyclic nucleotides. It was demonstrated recently, by using the 5-hydroxytryptamine (5-HT)2 receptor antagonist ketanserin and the 5-HT3 receptor antagonist tropisetron, that 5-HT acts as an important mediator in cholera toxin- and heat stable E. coli enterotoxin-induced fluid secretion. In the present investigation ketanserin and tropisetron were compared with the newer 5-HT3 receptor antagonists ondansetron and granisetron versus 5-HT-, cholera toxin- and heat stable E. coli enterotoxin-induced fluid secretion in the rat jejunum in vivo. Both ondansetron and granisetron dose-dependently inhibited 5-HT- and enterotoxin-induced fluid secretion. Ketanserin blocked 5-HT-induced fluid secretion, but only diminished enterotoxin-induced effects even at higher doses. Tropisetron inhibited 5-HT- and cholera toxin-induced effects at high dose but only diminished heat stable E. coli enterotoxin-induced effects. We conclude that 5-HT3 receptors, located on enterochromaffin cells and nervous structures, are more important in mediating fluid secretion than 5-HT2 receptors, located on the epithelial cells.
Beubler
E
E
Department of Experimental and Clinical Pharmacology, Karl-Franzens-University, Graz, Austria.
Schirgi-Degen
A
A
Gamse
R
R
D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology*; D001826:Body Fluids / Q000378:metabolism*; D002772:Cholera Toxin / Q000494:pharmacology; D004768:Enterotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D029968:Escherichia coli Proteins; D005260:Female; D017829:Granisetron / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007583:Jejunum / Q000187:drug effects* / Q000378:metabolism; D007650:Ketanserin / Q000494:pharmacology; D017294:Ondansetron / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000077526:Tropisetron
D001427:Bacterial Toxins; D002772:Cholera Toxin; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D017829:Granisetron; D007211:Indoles; D007650:Ketanserin; D017294:Ondansetron; D011985:Receptors, Serotonin; D012701:Serotonin; D012702:Serotonin Antagonists; D000077526:Tropisetron; C034151:heat stable toxin (E coli)