DEFECTIVE MODULATION OF COLONIC SECRETOMOTOR NEURONS IN A RABBIT MODEL OF COLITIS

The present in vitro study was conducted to investigate possible alter ations in the control of colonic electrolyte transport in an experimen tal model of colitis. Intrarectal administration of trinitrobenzenesul fonic acid induced a colitis-like inflammation in the rabbit distal co lon. Responses to amiloride and residual short-circuit current after t his treatment were unchanged, suggesting that the absorptive and secre tory mechanisms remained intact. Electrical field stimulation and vaso active intestinal polypeptide, a candidate secretomotor neurotransmitt er, both elicited similar responses in control and colitic tissue. Thi s suggests that communication at the neuroepithelial junction was unim paired. In untreated tissue, the effects of prostaglandin E2 (PGE2) an d of acetylcholine were attenuated by tetrodotoxin, suggesting, theref ore, that both play a role in the modulation of secretomotor neurons. In addition, PGE2 had an appreciable direct epithelial effect. Respons es to both of these agonists were absent in colitis. The effects of N6 ,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate were unchanged in colitis, suggesting that altered PGE2 responsiveness may involve chang es in epithelial receptor number, affinity, or in their ability to med iate an increase in adenosine 3',5'-cyclic monophosphate levels. It is concluded that this rabbit model of colitis exhibits 1) defects in th e modulation of secretomotor neurons by acetylcholine and PGE2 and 2) an attenuated epithelial response to PGE2.