Saito M, Nishi K, Fukumoto Y, Weiss R M, Latifpour J
Section of Urology, Yale University School of Medicine, New Haven, CT 06520, USA.
Biochem Pharmacol. 1996 Nov 22;52(10):1593-8. doi: 10.1016/s0006-2952(96)00565-5.
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 (D8), 8 weeks age-matched control (C8), 16 weeks diabetic (D16), 16 weeks diabetic-insulin-treated (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). 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 D8, C8, D16, DI16, and C16 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 (ETA selective), ET-3 (ETC selective), and IRL 1620 (ETB 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 and was consistent with the predominance of the ETA 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.
由于越来越多的证据表明糖尿病会引起血浆中内皮素（ETs）水平的变化以及外周组织中ET受体特性的改变，并且有报道指出在哺乳动物的输精管中存在大量的ET受体，我们研究了以下几组大鼠输精管中ET受体特性可能的改变：8周龄糖尿病大鼠（D8）、8周龄年龄匹配的对照大鼠（C8）、16周龄糖尿病大鼠（D16）、16周龄糖尿病胰岛素治疗大鼠（糖尿病发病8周后开始治疗）（DI16）以及16周龄年龄匹配的对照大鼠（C16）。通过静脉注射65mg/kg链脲佐菌素（STZ）诱导糖尿病。糖尿病大鼠出现高血糖、低胰岛素血症、糖尿、多饮和多尿，并且其输精管比对照大鼠和糖尿病胰岛素治疗大鼠的小。用[125I]ET-1进行的受体结合实验表明，D8、C8、D16、DI16和C16组动物输精管中ET受体的密度分别为377±11、255±24、315±18、210±12和214±7fmol/mg蛋白质。ET-1（非选择性）、BQ 610（ETA选择性）、ET-3（ETC选择性）和IRL 1620（ETB选择性）可抑制[125I]ET-1与ET受体的结合，其Ki值的排序如下：ET-1 < BQ 610 < ET-3 << IRL 1620。所有组中ET受体的药理学特征相似，并且与大鼠输精管中ETA受体亚型占主导地位一致。我们的数据表明，实验性糖尿病上调了大鼠输精管中ET受体的密度，并且胰岛素治疗可逆转这种受体上调。
