Saito M, Weiss R M, Latifpour J
Department of Urology, Tottori University Faculty of Medicine, Yonago, Japan.
Int J Urol. 1999 Jul;6(7):361-8. doi: 10.1046/j.1442-2042.1999.00074.x.
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.
本研究旨在探讨胰岛素治疗对糖尿病诱导的大鼠输尿管内皮素（ET）受体改变的影响。
检测以下几组大鼠输尿管中ET受体的生化特性：8周糖尿病组（D8）；8周龄匹配对照组（C8）；16周糖尿病组（D16）；16周糖尿病胰岛素治疗组（糖尿病发病8周后开始胰岛素治疗）（DI16）；以及16周龄匹配对照组（C16）。通过静脉注射65mg/kg链脲佐菌素（STZ）诱导糖尿病。
用[125I]-ET-1饱和实验测定，D8、C8、D16、DI16和C16组输尿管质膜中ET受体的密度（Bmax值）分别为91.7±10.1、42.1±7.2、71.1±2.4、51.5±6.3和45.1±3.3fmol/mg蛋白质。ET-1（非选择性）、ET-3（ET(B/C)选择性）、BQ610（ET(A)选择性）和IRL 1620（ET(B)选择性）抑制[125I]-ET-1与大鼠输尿管膜微粒中ET受体的结合，其Ki值的顺序如下：ET-1 < BQ 610 < ET-3 << IRL 1620。在所有检测组中，ET受体的药理学特征相似，且与输尿管膜微粒中ET(A)受体亚型占优势一致。通过在克隆的人ET(A)和ET(B)受体中进行类似结合研究获得的抑制数据，证实了输尿管组织中ET受体的亚型特异性。
数据表明，糖尿病导致大鼠输尿管中ET受体上调，而胰岛素治疗可使其恢复正常。
