ABNORMALITIES IN THE CONTRACTILE PROPERTIES OF COLONIC SMOOTH-MUSCLE IN IDIOPATHIC SLOW TRANSIT CONSTIPATION

Background The underlying pathophysiology of idiopathic slow transit c onstipation (ISTC) remains unclear. At present, there is little eviden ce to implicate a smooth muscle myopathy in the aetiology of this cond ition. This study compared the effect of cisapride on the cholinergic response of colonic muscle strips from patients with this condition wi th that of control tissue. Methods Isometric tension production was re corded from circular smooth muscle strips taken from five patients und ergoing colectomy for ISTC in response to cumulative concentrations of carbachol (100 nmol/l-100 mu mol/l) alone and in the presence of cisa pride 400 nmol/l. Similar dose-response activity was obtained for a co ntrol group consisting of six patients undergoing resection fur colore ctal carcinoma. Results In the absence of cisapride, smooth muscle fro m patients with carcinoma exhibited a significantly lower sensitivity to cholinergic stimulation (agonist concentration required to produce half-maximal activation (EC(50)) 4.83 mu mol/l) than that from patient s with ISTC (EC(50) 1.63 mu mol/l, P = 0.036), and also a greater maxi mal frequency of the oscillatory activity associated with the increase in isometric tension (0.070 versus 0.049 Hz, P = 0.035). Cisapride ha d no effect on the sensitivity to carbachol of the carcinoma tissue bu t brought about a significant reduction in the sensitivity of smooth m uscle from patients with ISTC (EC(50) 3.24 mu mol/l, P = 0.043). Concl usion These findings indicate that colonic smooth muscle from patients with ISTC is hypersensitive to cholinergic stimulation and suggest th e existence of a smooth muscle myopathy in this condition.