Study Of The Mechanism In Low Response To The Acetylcholine And Isoproterenol In Catharitic Colon

Background/Purpose:Slow transit constipation(STC) is a disorder of colonic motility characteized by a reduction in the frequency, amplityde and duration of propulsive contractions in the large bowel. The disorder spans a spectrum of variable severity, ranging from patients who have relatively mild delays in transit but who are otherwise indistinguishable from irritable bowel syndrome patients at one extreme, to patients with colonic inertia or chronic megacolon at the other extreme. Current medical treatments for STC are often ineffective, and the outcome of surgery is unpredictable. STC was first described almost a century ago. Since this time, progress in improving therapy for this condition has been complicated by a lack of understanding of the aetiology, and great variation in the methods and criteria used for the study of patients with this debilitating disorder. It is difficult to find unequivocal data, and harder still to give a definitive picture of the cause or causes of STC. It has been shown that predominant symptoms in STC correlate with nervous system abnormalities, gut hormone responses and intestinal myopathy in several clinical experiments. In present there is little evidence to implicate a smooth muscle myopathy in the aetiology of this condition, although a defective cholinergic innervation has been postulated. We tested the hypothesis that cholinergic and adrenergic colonic innervation is deranged in this condition by comparing the effect of acetylcholine and isoproterenol on the response of colonic muscle strips from patients and rat model complaining of slow transit constipation with thiscondition with that of control tissue in order to find an appropriate interpretation of changes in the patients suffered from constipation.Methods:To investigate the motility and electromyogram of cathartic colon, we we feed the rats with rhubarb for 3 months. Serosal recordings of colonic myoelectrical activity,suspension muscle strips test and radioreceptor assay(RBA) were made in STC rats with examined the intestinal transit function, colonic electromyogram and receptor functions in comparing different effect of acetylcholine(Ach) and isoproterenol(ISO) on the response of colonic smooth muscle with that control tissue.Isometric tension production was also recorded from circular and longitudinal smooth muscle strips taken from nine patients undergoing colectomy for STC in response to separated concentrations of acetylcholine and isoproterenol. Similar dose-response activity was obtained for a control group consisting of seven patients undergoing resection for rectal cancer.Results:1. The abnormal character of the contraction of colon muscle strips and the change of muscarine cholinoceptor M and adrenoceptor βin STC patient is according with rat model of STC from statistical analysis. It demonstrated that the model fit propert of STC in occurrenc, develop and Lesion. The results indicate that chronic application of stimulant laxatives can induce disorganization of dynamic and injure enteric nervous system.2. After treating with rhubarb for 3 months. The amplitude of slow wave and muscle strips in vitro were decreased. Also the reaction to acetylcholine(Ach) and isoprotereno were depressed in the cathartic colon and the content of cholinoceptor M and adrenoceptor β in the intestinal of cathartic colon rats was decreased significantly compared to control group.3. Colonic smooth muscle from patients with STC is low sensitivity tocholinergic and adrenergic stimulation resulted from the loss of M and βreceptors and suggest the existence of a smooth muscle myopathy in this condition. 4. The study suggests that the incoordinated contractions in colon may be one of the predominant mechanism of constipation. Conclusions:These findings indicate that the abnormalities of receptors are responsible for STC. But the pathophysiology of slow transit constipation is complex and not easily approached through datas from animals alone. Further studies using demi...