5-HT receptor antagonists and heat-stable Escherichia coli enterotoxin-induced effects in the rat.
The effect of heat-stable E. coli enterotoxin on intestinal fluid secretion is commonly considered to be mediated by stimulation of mucosal cyclic guanosine monophosphate (cGMP). It was demonstrated recently that 5-hydroxytryptamine (5-HT) acts as an important mediator in cholera toxin-induced fluid secretion. To elucidate the possible involvement of 5-HT in the secretory response to heat-stable E. coli enterotoxin, in vivo experiments were performed in the rat jejunum. The inhibitory effects of the 5-HT2 receptor antagonist ketanserin, the 5-HT3 receptor antagonist tropisetron and indomethacin were studied in heat-stable E. coli enterotoxin-induced fluid secretion. Tropisetron and ketanserin (100 micrograms/kg each) alone only partially reduced the secretory effect of the toxin. However, in combination, the two blockers (100 plus 100 micrograms/kg) significantly reduced and at 200 plus 200 micrograms/kg totally abolished heat-stable E. coli enterotoxin-induced secretion without influencing the enterotoxin-induced increase in cGMP. Pretreatment with indomethacin (10 mg/kg) reduced the secretory response to the enterotoxin by about 50%. These results support the concept that 5-HT is an important mediator in intestinal fluid secretion induced by heat-stable E. coli enterotoxin. The enterotoxin may use 5-HT to stimulate prostaglandin formation via 5-HT2 receptors and to activate neuronal structures via 5-HT3 receptors.
Beubler
E
E
Department of Experimental and Clinical Pharmacology, Karl-Franzens-University, Graz, Austria.
Badhri
P
P
Schirgi-Degen
A
A
D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology*; D006152:Cyclic GMP / Q000096:biosynthesis*; D004768:Enterotoxins / Q000494:pharmacology*; D029968:Escherichia coli Proteins; D005260:Female; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology; D007279:Injections, Subcutaneous; D007413:Intestinal Mucosa / Q000737:chemistry / Q000378:metabolism; D007583:Jejunum / Q000187:drug effects* / Q000378:metabolism; D007650:Ketanserin / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists; D000077526:Tropisetron
D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007211:Indoles; D012702:Serotonin Antagonists; C034151:heat stable toxin (E coli); D000077526:Tropisetron; D007650:Ketanserin; D006152:Cyclic GMP; D007213:Indomethacin