Molecular mediators formed in the small intestine in response to cholera toxin.
The molecular mechanism of experimental cholera, leading to increased water and electrolyte secretion, was evaluated with the rabbit intestinal loop model. The levels of cyclic adenosine monophosphate (cAMP), prostaglandin E2 (PGE2), and 5-hydroxytryptamine (5-HT) were measured in mucosal tissue or luminal fluids from intestinal segments exposed to cholera toxin (CT). Each mediator increased in a dose-dependent manner coinciding with the amount of fluid accumulating in the CT-treated loops within the 16 h observation period. Interestingly, a substantial amount of the cAMP in the CT loops was released into the intestinal lumen, along with the fluid. Fluid accumulation was evoked by instillation of PGE2 and CT into the intestinal segments, but not by 5-HT. Large doses of dibutyryl cAMP at 50 mg/ml, but not at 25 mg/ml, also evoked fluid accumulation when injected into the intestine. Further, CT evoked the release of 5-HT from the mucosa, although the high doses of cAMP caused a massive release of 5-HT. PGE2 injection was without effect on 5-HT release. Although CT increased the amount of PGE2 into the luminal fluid, no effect on PGE2 levels was observed by injecting any dose of dibutyryl cAMP or 5-HT into the intestinal lumen. Our interpretation of these data is that CT stimulates the independent synthesis and release of both cAMP and PGE2. The cAMP appears to cause the release of 5-HT from the enterochromaffin cells. Since dibutyryl cAMP did not evoke a PGE2 response, it was concluded that cAMP could elicit secretion of fluid without the participation of PGE2; however, the cAMP doses were not physiological.(ABSTRACT TRUNCATED AT 250 WORDS)
Peterson
J W
JW
Department of Microbiology, University of Texas Medical Branch, Galveston 77555-1019.
Cantu
J
J
Duncan
S
S
Chopra
A K
AK
D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism* / Q000502:physiology; D003967:Diarrhea / Q000378:metabolism; D004195:Disease Models, Animal; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism*; D011458:Prostaglandins E / Q000378:metabolism* / Q000502:physiology; D011817:Rabbits; D012701:Serotonin / Q000378:metabolism* / Q000502:physiology
D011458:Prostaglandins E; D012701:Serotonin; D002772:Cholera Toxin; D000242:Cyclic AMP