Diabetes-related changes in contractile responses of stomach fundus to endothelin-1 in streptozotocin-induced diabetic rats

The contractile response of the stomach fundus to endothelin-1 (ET-1) was examined in streptozotocin (STZ)-induced diabetic rats. In STZ-diabetic rats (versus age-matched control rats) (a) ET-1 caused a longer-lasting contraction of stomach fundus strips, and (b) in the dose-response curve, the ET-1-induced contraction was significantly greater for a given concentration (3 × 10-7 to 10-7 M). Although repeated application of ET-1 led to desensitization, the desensitization was less pronounced in STZ-diabetic rats than in the controls. The density of the binding sites for [125I]-ET-1 was increased in the diabetic stomach fundus (versus the controls), but Kd values were similar between the two groups. The ETB receptor mRNA expression level was significantly increased in the diabetic stomach fundus. These results suggest that the diabetes-related enhancement of the ET-1-induced contraction of the stomach fundus may be due to an increase in the ETB receptor population.