EFFECTS OF DIABETES-MELLITUS ON THE CONTRACTILE ACTIVITY OF CARBACHOLAND GALANIN IN ISOLATED GASTRIC FUNDUS STRIPS OF RATS

The role of the cholinergic and peptidergic pathways in the impairment of gastric motility associated with diabetic gastroparesis was assess ed at: the postsynaptic level using isolated fundus smooth muscle stri ps. Maximal contractile responses to carbachol and galanin were signif icantly decreased in fundus strips isolated from rats rendered diabeti c by a single intraperitoneal injection of streptozotocin (STZ, 70 mg/ kg) 1, 4 and 8 weeks before experiments. We also observed notable decr ements in the slopes and Hill's coefficients without conspicuous chang es in the EC50 of the respective galanin concentration-response curves measured in strips obtained from STZ animals after 4 and 8 weeks. L-N AME reversed the above-mentioned alterations in an L-arginine-sensitiv e manner in STZ rats after 4 weeks but not in STZ rats after 8 weeks, The blood plasma nitrite/nitrate levels in STZ animals after 4 and 8 w eeks were increased by 44.6 and 61.9%, respectively. Ca2+-independent nitric oxide synthase activity in gastric fundus strips and stomach co rpus mucosa from STZ rats after 4 weeks was markedly enhanced by 37.4 and 31.9%, respectively, suggesting an enhanced nitric oxide productio n. In vivo insulin treatment prevented diabetes-induce alterations in smooth muscle contractility. We conclude that the smooth muscle dysfun ction evoked by experimental diabetes causing diminished contractions of fundus strips to carbachol and galanin is at least partly due to th e increased nitric oxide synthesis.