Colitis affects the smooth muscle and neural response to motilin in the rabbit antrum

Background and purpose: The underlying mechanisms of gastric dysfunction during or after an episode of intestinal inflammation are poorly understood. This study investigated the effects of colitis on the contractile effects of motilin, an important endocrine regulator of gastric motility, in the antrum. Experimental approach: Myeloperoxidase (MPO) activity, NF-kappa B activity and motilin receptor density were determined in the antrum of rabbits 5 days after the induction of 2,4,6-trinitrobenzenesulphonic acid colitis. Smooth muscle and neural responses to motilin were studied in antral smooth muscle strips in vitro. Key results: Colitis did not affect MPO activity, but increased NF-kappa B activity in the antrum. Motilin receptor density in the antrum was not affected. Under control conditions, motilin induced a slowly developing tonic smooth muscle contraction. Five days post-inflammation, tonic contractions to motilin were reduced and preceded by a rapid initial contraction. Other kinases were recruited for the phosphorylation of myosin light chain (MLC) (a multi-functional MLC kinase), and for the inhibition of MLC phosphatase (Rho kinase in addition to protein kinase C) to mediate the motilin-induced contractions during inflammation. Colitis potentiated the cholinergic neural on-contractions in the antrum. This was associated with a hyper-reactivity to motilin and an increased muscle response to ACh. Conclusions and implications: Colitis altered the course of the motilin-induced smooth muscle contraction in the antrum. This involved changes in the kinases phosphorylating MLC. Increased cholinergic excitability to motilin in the antrum may play a role in the pathogenesis of inflammation-associated gastric motility disorders. British Journal of Pharmacology (2010) 159, 384-393; doi: 10.1111/j.1476-5381.2009.00537.x; published online 4 December 2009