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糖尿病大鼠膀胱顶部内皮素受体的基因表达、定位及药理学特性

Gene expression, localization, and pharmacological characterization of endothelin receptors in diabetic rat bladder dome.

作者信息

Saito M, Wada Y, Ikeda K, Wang Z, Smith S D, Foster H E, Nishi K, Weiss R M, Latifpour J

机构信息

Section of Urology, Yale University School of Medicine, P.O. Box 208041, 333 Cedar Street, New Haven, CT 06520, USA.

出版信息

Eur J Pharmacol. 2000 Jan 17;387(3):253-63. doi: 10.1016/s0014-2999(99)00753-0.

DOI:10.1016/s0014-2999(99)00753-0
PMID:10650170
Abstract

As there are significant amounts of functional endothelin receptors in the mammalian urinary tract, we examined the effect of experimental diabetes on the expression of endothelin receptors and their mRNAs in the rat bladder dome. The density of endothelin receptors in the rat bladder dome was higher (8 and 16 weeks following the onset of diabetes) than in age-matched controls. Insulin treatment, started 8 weeks after the induction of diabetes, partially reversed the endothelin receptor alterations. The pharmacological profile of the endothelin receptors in the bladder dome was similar in all groups and was consistent with the predominance of the endothelin ET(A) receptor subtype (ET(A):ET(B)=approximately 4:1). Autoradiographic studies demonstrated that the endothelin receptors were located in all tissue components of the bladder, including epithelial and muscular layers. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) data indicated that diabetes increased the expression level of gene transcripts for both endothelin receptor subtypes and that insulin treatment reversed the mRNA upregulation.

摘要

由于哺乳动物尿路中存在大量功能性内皮素受体,我们研究了实验性糖尿病对大鼠膀胱顶部内皮素受体及其mRNA表达的影响。糖尿病发病后8周和16周时,大鼠膀胱顶部内皮素受体的密度高于年龄匹配的对照组。糖尿病诱导8周后开始的胰岛素治疗部分逆转了内皮素受体的改变。所有组膀胱顶部内皮素受体的药理学特征相似,且与内皮素ET(A)受体亚型占优势一致(ET(A):ET(B)约为4:1)。放射自显影研究表明,内皮素受体位于膀胱的所有组织成分中,包括上皮层和肌肉层。半定量逆转录-聚合酶链反应(RT-PCR)数据表明,糖尿病增加了两种内皮素受体亚型基因转录本的表达水平,而胰岛素治疗逆转了mRNA的上调。

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