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[大鼠中缓激肽肾小球受体的证据。钠摄入对受体密度和亲和力的影响]

[Evidence for a glomerular receptor for bradykinin in rats. Effect of sodium intake on density and affinity of the receptor].

作者信息

Bascands J L, Emond C, Cabos-Boutot G, Pécher C, Suc J M, Girolami J P

机构信息

INSERM U 133, faculté de médecine, Toulouse.

出版信息

Arch Mal Coeur Vaiss. 1989 Jul;82(7):1219-22.

PMID:2554836
Abstract

Bradykinin (BK) have been involved in a lot of pharmacological and biological effects including natriuresis, vasodilatation, inflammation and pain mediation. All these potent effects of BK are presumably mediated via one or more specific receptors which have been classified in two types named B1 and B2 receptors. In the kidney, specific binding have been reported successively in cortical epithelial membranes, in renomedullary interstitial cells and in cortical collecting tubules. Furthermore, since a large number of vasoactive compounds have been shown to regulate renal glomerular hemodynamics, we examined the binding of BK in rat glomerular membranes and the effect of variable salt diet on the density (Bmax) and the dissociation constant (KD) of this binding. Incubation of a radiolabeled bradykinin analog, [125I]-Tyr8-BK with a crude membrane preparation obtained from isolated rat glomeruli revealed a time dependent binding. The binding was saturable, reversible and was a linear function of protein membrane concentration. The radiolabeled Tyr8-BK bound to a single class of binding sites with an equilibrium dissociation constant (KD) of 2.75 +/- 0.7 nM and a density (Bmax) of 32.1 +/- 5.2 fmol/mg protein. [125I]-Tyr8-BK binding was reversed by bradykinin (Ki = 0.4 10(-9) M) and by other kinin analogs. However, Des-Arg9-BK had no effect on binding of the radiolabelled BK. These results are consistent with the presence of a B2-kinin like receptor in rat glomeruli. Low salt diet (during one month) and water deprivation (during 4 days) induced a decrease in the density of glomerular BK like receptors respectively (Bmax = 12.45 +/- 1.3 and 13.25 +/- 1.17 fmol/mg protein).(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

缓激肽(BK)具有多种药理和生物学作用,包括利钠、血管舒张、炎症和疼痛介导。BK的所有这些强效作用可能是通过一种或多种特定受体介导的,这些受体已被分为B1和B2两种类型。在肾脏中,已相继报道在皮质上皮细胞膜、肾髓质间质细胞和皮质集合管中有特异性结合。此外,由于大量血管活性化合物已被证明可调节肾小球血流动力学,我们研究了BK在大鼠肾小球膜中的结合情况以及不同盐饮食对这种结合的密度(Bmax)和解离常数(KD)的影响。用从分离的大鼠肾小球获得的粗膜制剂与放射性标记的缓激肽类似物[125I]-Tyr8-BK孵育,显示出时间依赖性结合。这种结合是可饱和的、可逆的,并且是蛋白质膜浓度的线性函数。放射性标记的Tyr8-BK与一类结合位点结合,平衡解离常数(KD)为2.75±0.7 nM,密度(Bmax)为32.1±5.2 fmol/mg蛋白质。缓激肽(Ki = 0.4×10^(-9) M)和其他激肽类似物可逆转[125I]-Tyr8-BK的结合。然而,去-精氨酸9-缓激肽对放射性标记的缓激肽的结合没有影响。这些结果与大鼠肾小球中存在B2类激肽受体一致。低盐饮食(持续一个月)和禁水(持续4天)分别导致肾小球BK样受体密度降低(Bmax = 12.45±1.3和13.25±1.17 fmol/mg蛋白质)。(摘要截短于250字)

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