Effects of insulin treatment on diabetes-induced alterations in endothelin receptors in rat ureter.

Abstract

The present investigation was undertaken to examine the effect of insulin treatment on diabetes-induced alterations in endothelin (ET) receptors in rat ureters. The biochemical properties of ET receptors were examined in rat ureters from the following groups: 8 weeks diabetic (D8); 8 weeks age-matched control (C8); 16 weeks diabetic (D16); 16 weeks diabetic-insulin treated (insulin started 8 weeks after the onset of diabetes) (DI16); and 16 weeks age-matched control (C16). Diabetes was induced by the i.v. injection of 65 mg/kg streptozotocin (STZ). The densities of ET receptors (Bmax values), as determined by saturation experiments with [125I]-ET-1, in the ureteral plasma membranes of D8, C8, D16, DI16 and C16 were 91.7 +/- 10.1, 42.1 +/- 7.2, 71.1 +/- 2.4, 51.5 +/- 6.3 and 45.1 +/- 3.3 fmol/mg of protein, respectively. [125I]-ET-1 binding to the ET receptors in rat ureteral membrane particulates was inhibited by ET-1 (non-selective), ET-3 (ET(B/C selective), BQ610 (ET(A) selective) and IRL 1620 (ET(B) selective) with the following rank order of Ki values: ET-1 < BQ 610 < ET-3 << IRL 1620. The pharmacological profile of the ET receptors was similar in all groups examined and was consistent with the predominance of the ET(A) receptor subtype in the ureteral membrane particulates. The subtype specificity of ET receptors in the ureteral tissues is confirmed with inhibition data obtained from similar binding studies in cloned human ET(A) and ET(B) receptors. The data indicate that diabetes results in an up-regulation of ET receptors in the rat ureter, which is normalized by insulin treatment.