Rat Colonic Motor Responses to Inflammatory Mediators In Vitro: A Poor Model for the Human Colon

Abstract

There is evidence that the rat colon exposed to trinitrobenzenesulfonic acid (TNBS) develops a colitis‐like inflammation which may be a model for inflammatory bowel disease (IBD) in humans. The aim of this study was to determine if the pharmacologic responses of the normal rat distal colon to several IBD‐associated inflammatory mediators were sufficiently similar to those of the normal human colon for the rat with TNBS‐induced colitis to provide an appropriate model for their effects on human colonic motility in IBD. Longitudinal and circular muscle mechanical properties were also investigated. Longitudinal muscle responded with concentration‐dependent contractions to histamine, leukotriene D4, and prostaglandins E2 and F‐2α, which were mediated by a direct action. In general, circular muscle responses to these mediators were smaller, and in the cases of leukotriene D4 and prostaglandin F2α, these were modulated by the concurrent activation of intrinsic inhibitory neurons. The mechanical properties of rat distal colonic longitudinal and circular muscle differed significantly from the equivalent human muscles. In most aspects studied normal rat distal colonic smooth muscles were at variance with previously reported properties of the equivalent human muscles. Thus the rat colon would be inappropriate as a model to study potential inflammatory mediator‐induced alterations of colonic motility in IBD.