Praddaude F, Tack I, Emond C, Bascands J L, Girolami J P, Tran-Van T, Regoli D, Ader J L
Laboratory of Physiology Faculty of de Medicine, Toulouse, France.
Eur J Pharmacol. 1995 Dec 27;294(1):173-82. doi: 10.1016/0014-2999(95)00532-3.
We investigated the effects of bradykinin on glomerular bradykinin B2 receptor functions and parameters in vivo, after intrarenal infusion of bradykinin, and in vitro, after incubation of isolated rat glomeruli with bradykinin. Bradykinin transiently increased renal plasma flow whereas a second challenge was ineffective. Scatchard analysis demonstrated the presence of two populations of bradykinin binding sites whose densities were similarly decreased by about 40% after intrarenal bradykinin infusion. This decrease was not altered by an acid wash suggesting internalization of the radiolabelled ligand. The effect of bradykinin was prevented by a bradykinin B2 receptor antagonist. Pre-exposure of isolated rat glomeruli to bradykinin mimicked the in vivo results because there was a reduction in bradykinin-induced prostaglandin E2 and prostaglandin F2 alpha release. Rapid recovery was observed 15 min after washing out the bradykinin. Our results directly demonstrate a negative homologous down-regulation of B2 glomerular bradykinin receptor density under both in vivo and in vitro conditions, an effect which involves a rapid sequestration of the receptor.
我们研究了缓激肽对体内肾小球缓激肽B2受体功能和参数的影响（肾内输注缓激肽后），以及体外影响（分离的大鼠肾小球与缓激肽孵育后）。缓激肽使肾血浆流量短暂增加，而第二次刺激则无效。Scatchard分析表明存在两类缓激肽结合位点，肾内输注缓激肽后其密度同样降低约40%。酸洗未改变这种降低，提示放射性标记配体的内化。缓激肽B2受体拮抗剂可阻止缓激肽的作用。将分离的大鼠肾小球预先暴露于缓激肽可模拟体内结果，因为缓激肽诱导的前列腺素E2和前列腺素F2α释放减少。洗去缓激肽15分钟后观察到快速恢复。我们的结果直接证明了在体内和体外条件下，B2肾小球缓激肽受体密度均出现负向同源下调，这一效应涉及受体的快速隔离。
