Species-differences in diabetes-induced alterations in vasa deferentia endothelin receptors

Abstract

As there is increasing evidence that diabetes induces changes in the plasma levels of endothelins (ETs) and the properties of the ET receptors in peripheral tissues and there are reports indicating the presence of significant amounts of endothelin binding sites in the mammalian vasa deferentia, we studied possible alterations in ET receptor characteristics in the vasa deferentia of rats and rabbits. Diabetes was induced with i.v. injections of streptozotocin (65 mg/kg) and alloxan (100 mg/kg) in rats and rabbits, respectively. We investigated the binding characteristics of endothelin (ET) receptors in the vasa deferentia of four and five month experimentally-induced diabetic rats and rabbits, respectively. The densities and pharmacological properties of ET receptors in the rat and rabbit vasa deferentia were examined by radioligand receptor binding studies using [125I]ET-1. Receptor binding experiments with [125I]ET-1 revealed a dramatic upregulation in the expression of a single class of specific, saturable, high affinity of [125I]ET-1 binding sites in the diabetic rats but not in the vasa deferentia of diabetic rabbits. ET-1 (non-selective), ET-3 (ETC selective), BQ 610 (ETA selective) and IRL 1620 (ETB selective) compounds inhibited [125I]ET-binding to the rats and rabbits vasa deferentia consistent with the predominance of ETA receptors in these tissues.