The potential role of chronic otilonium bromide administration in preventing colonic dysmotility induced by repeated water avoidance stress in rats

It has been shown that repeated water avoidance stress (rWAS) applied in rats induces changes in the colonic motility, similar to those described in Irritable Bowel Syndrome (IBS). Despite the wide use of otilonium bromide (OB) in the treatment of IBS, its mechanism of action has not been fully clarified yet.Aim of the present study was to investigate the effects of OB on colonic dysmotility induced by rWAS in Wistar rats. To this purpose, animals were distributed into four experimental groups: CTR (controls, untreated); OB-treated (orally treated with OB for 10 days); WAS (exposed to rWAS for 10 days); WAS+OB (exposed to rWAS and orally treated with OB for 10 days). Mechanical experiments were performed on full-thickness muscle strips from the distal colon, cut in the circular direction, mounted in organ baths for isometric recording of the spontaneous mechanical activity. The majority of strips from CTR, exhibited high amplitude contractions superimposed on smaller ones, similarly to OB-treated and WAS+OB rats. In WAS rats, the amplitude of the spontaneous motility pattern was greatly reduced and no high amplitude contractions were observed. In all groups and especially in the WAS one, tetrodotoxin (TTX) or L-NG-nitro arginine (L-NNA) increased the amplitude of the spontaneous contractions, thus indicating the removal of a nitrergic nervous control. Methacholine caused a similar contractile response in CTR and WAS but it was ineffective in OB-treated and WAS+OB rats. Immunohistochemical experiments are in progress to correlate morphological with functional data. From the present results it appears that OB, other than interacting with the muscular muscarinic receptors, prevents colonic dismotility induced by WAS, likely interfering with nitric oxide production/release.