Motilin receptor density in inflamed and noninflamed tissue in rabbit TNBS-induced colitis.

Trinitrobenzenesulphonic acid (TNBS)-induced colitis decreases the contractile response of the rabbit colon to motilin, and inflammation may increase plasma motilin levels. We studied whether the decreased contractility could be due to a down-regulation of motilin receptors, caused by increased plasma motilin levels. As this would affect all tissues, uninflamed sites were studied as well. Colitis was induced by different doses (100-150 mg kg-1) of TNBS. In the colon, the TNBS dose-dependent decrease of the contractile response towards motilin was reflected in a decrease in motilin receptor density. In contrast, in the antrum, receptors were upregulated by 150 mg kg-1 TNBS, while central motilin receptors in the cerebellum were not affected. Plasma motilin levels were not influenced by inflammation, although the motilin content and mRNA expression in the duodenal and jejunal mucosa, but not in the colon, was significantly increased. The opposite was true for interleukin-1beta and interleukin receptor antagonist mRNA expression. We conclude that the decreased motilin contractility in rabbit colitis is due to a downregulation of motilin receptors in the colon, but this is not caused by chronic hormonal stimulation.