Girolami J P, Emond C, Bascands J L
INSERM U 133, Institut Louis Bugnard, Faculté de Médecine Rangueil, Toulouse, France.
Agents Actions Suppl. 1992;38 ( Pt 2):23-30.
Using binding techniques we identified specific B2 kinin binding sites showing a pharmacological profile similar in glomeruli and in mesangial cell. Scatchard analysis revealed two classes of binding sites: a very-high-affinity site (Kd = 0.44 nM) and a high affinity site (Kd = 6.3 nM). Activation of the BK receptor of mesangial cells is associated with i) a transient dose-dependent increase in inositol 1,4,5 Triphosphate, ii) a biphasic rise in cytosolic free calcium, iii) a progressive secretion of PGE2, iv) an inhibition of the PGE2-stimulated increase of cAMP formation. All these effects were prevented by B2 antagonists. This multiple signal transduction pathway could suggest either heterogeneity in the BK receptor of the mesangial cell or different biological responses to be identified. Taken together, the results indicate that BK, at least in cultured cells, acts as a contractile effector, however, the physiological significance of a kinin receptor in the glomerulus remains to be elucidated.
我们运用结合技术鉴定出了特定的B2激肽结合位点,这些位点在肾小球和系膜细胞中呈现出相似的药理学特征。Scatchard分析揭示出两类结合位点:一个极高亲和力位点(解离常数Kd = 0.44 nM)和一个高亲和力位点(Kd = 6.3 nM)。系膜细胞BK受体的激活与以下情况相关:i)肌醇1,4,5-三磷酸出现短暂的剂量依赖性增加;ii)胞质游离钙呈双相升高;iii)前列腺素E2(PGE2)进行性分泌;iv)对PGE2刺激的环磷酸腺苷(cAMP)形成增加产生抑制作用。所有这些效应均被B2拮抗剂阻断。这种多重信号转导途径可能表明系膜细胞BK受体存在异质性,或者存在有待确定的不同生物学反应。综合来看,结果表明BK至少在培养细胞中作为一种收缩效应物发挥作用,然而,激肽受体在肾小球中的生理意义仍有待阐明。