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大鼠肾小球血栓素受体位点的特征分析

Characterization of glomerular thromboxane receptor sites in the rat.

作者信息

Wilkes B M, Solomon J, Maita M, Mento P F

机构信息

Department of Medicine, North Shore University Hospital, Manhasset, New York 11030.

出版信息

Am J Physiol. 1989 Jun;256(6 Pt 2):F1111-6. doi: 10.1152/ajprenal.1989.256.6.F1111.

Abstract

The aim of this study was to identify and characterize thromboxane (Tx) receptor sites in renal glomeruli. Binding studies were performed on freshly isolated glomeruli using the stable TxA2 receptor antagonist, [3H]SQ 29548. Specific binding was saturable, reversible, and varied with glomerular protein. Scatchard plots revealed a single class of high-affinity receptor sites (Kd = 14.3 +/- 2.4 nM, Bmax = 361 +/- 22 fmol/mg; n = 5). Specific binding was inhibited by Tx agonists (U-46619 and U-44069) and antagonist (SQ 29548) and was highly specific for Tx, since prostaglandin (PG)E2 and PGF2 alpha were 1,000-fold less potent in inhibiting binding. In vivo, U-46619 (1.75 micrograms.kg-1.min-1) was without effect on mean arterial pressure, but reduced renal blood flow by 71% (P less than 0.01) and glomerular filtration rate by 67% (P less than 0.01) and increased filtration fraction by 24% (P less than 0.05). SQ 29548 (10 micrograms.kg-1.min-1) completely blocked the renal effects of U-46619. These studies demonstrate the presence of specific receptor sites for Tx on renal glomeruli that are linked to modulation of renal hemodynamics.

摘要

本研究的目的是鉴定和表征肾肾小球中的血栓素(Tx)受体位点。使用稳定的TxA2受体拮抗剂[3H]SQ 29548对新鲜分离的肾小球进行结合研究。特异性结合具有饱和性、可逆性,且随肾小球蛋白而变化。Scatchard图显示存在一类高亲和力受体位点(Kd = 14.3 +/- 2.4 nM,Bmax = 361 +/- 22 fmol/mg;n = 5)。Tx激动剂(U-46619和U-44069)和拮抗剂(SQ 29548)可抑制特异性结合,且该结合对Tx具有高度特异性,因为前列腺素(PG)E2和PGF2α在抑制结合方面的效力低1000倍。在体内,U-46619(1.75微克·千克-1·分钟-1)对平均动脉压无影响,但使肾血流量减少71%(P < 0.01),肾小球滤过率减少67%(P < 0.01),滤过分数增加24%(P < 0.05)。SQ 29548(10微克·千克-1·分钟-1)完全阻断了U-46619的肾脏效应。这些研究表明肾肾小球上存在Tx特异性受体位点,其与肾血流动力学的调节有关。

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