Characterization of endothelin receptors in streptozotocin-induced diabetic rat vas deferens

Abstract

As there is increasing evidence that diabetes induces changes in the plasma levels of endothelins (ETs) and in the properties of ET receptors in peripheral tissues, and as there are reports indicating the presence of significant amounts of ET receptors in mammalian vasa deferentia, we studied possible alterations in ET receptor characteristics in the vasa deferentia of the following groups of rats: 8 weeks diabetic (D 8), 8 weeks age-matched control (C 8), 16 weeks diabetic (D 16), 16 weeks diabetic-insulin-treated (started 8 weeks after the onset of diabetes) (DI 16), and 16 weeks age-matched control (C 16). Diabetes was induced by the i.v. injection of 65 mg/kg streptozotocin (STZ). Diabetic rats had hyperglycemia, hypoinsulinemia, glucosuria, polydipsia, and polyuria and had smaller vasa deferentia than control and diabetic-insulin-treated animals. Receptor binding experiments with [ 125I]ET-1 demonstrated that the densities of ET receptors in vasa deferentia from D 8, C 8, D 16, DI 16, and C 16 animals were 377 ± 11, 255 ± 24, 315 ± 18, 210 ± 12, and 214 ± 7 fmol/mg of protein, respectively. [ 125I]ET-1 binding to the ET receptors was inhibited by ET-1 (non-selective), BQ 610 (ET A selective), ET-3 (ET C selective), and IRL 1620 (ET B selective) with the following rank order of K i values: ET-1 < BQ 610 < ET-3 ⪡ IRL 1620. The pharmacological profile of the ET receptors was similar in all groups and was consistent with the predominance of the ET A receptor subtype in the rat vasa deferentia. Our data indicate that experimental diabetes up-regulates the density of ET receptors in the rat vasa deferentia and that the receptor up-regulation is reversed by insulin treatment.