Néant F, Imbert-Teboul M, Bailly C
Laboratoire de Physiologie Rénale, Faculté Xavier Bichat, Université Paris 7, INSERM U 251, France.
J Clin Invest. 1994 Sep;94(3):1156-62. doi: 10.1172/JCI117431.
Since we have previously shown a direct inhibitory effect of platelet-activating factor (PAF) on Cl reabsorption in the medullary thick ascending limb of Henle's loop (TAL), the aim of this study was to extend this effect to the whole TAL and to further investigate the signaling pathway involved. In microperfused cortical TALs, PAF significantly decreased Cl reabsorption by 50.3 +/- 6.5%. On the one hand, this effect was not modified in the presence of staurosporine and was not mimicked by phorbol ester; chelating cytosolic Ca by BAPTA/AM failed to suppress the inhibitory effect of PAF on Cl reabsorption; moreover, no significant increase in intracellular Ca concentration could be observed in the presence of PAF on isolated tubules. On the other hand, 8-bromo cyclic GMP mimicked the PAF effect on Cl reabsorption and prevented a further effect of this agent; the PAF effect was significantly reduced by H-8, a cyclic GMP-dependent protein kinase inhibitor; in medullary TALs, PAF significantly increased by twofold cyclic GMP content, an effect inhibited by the PAF antagonist BN 50730, whereas PAF did not significantly modify cAMP content in basal or stimulated conditions. Finally, inhibition of nitric oxide production by NAME or NMMA failed to prevent the effect of PAF on Cl reabsorption. It is concluded that the PAF-induced inhibition of Cl reabsorption in the TAL was mediated by cyclic GMP, likely independent of a nitric oxide synthesis.
由于我们之前已证明血小板活化因子（PAF）对亨氏袢髓质厚升支（TAL）的氯离子重吸收有直接抑制作用，本研究的目的是将这种作用扩展至整个TAL，并进一步研究其涉及的信号通路。在微灌注的皮质TAL中，PAF使氯离子重吸收显著降低了50.3±6.5%。一方面，在存在星形孢菌素的情况下这种作用未被改变，佛波酯也未模拟该作用；用BAPTA/AM螯合胞质钙未能抑制PAF对氯离子重吸收的抑制作用；此外，在分离的肾小管中存在PAF时未观察到细胞内钙浓度有显著升高。另一方面，8-溴环鸟苷酸模拟了PAF对氯离子重吸收的作用并阻止了该药物的进一步作用；PAF的作用被环鸟苷酸依赖性蛋白激酶抑制剂H-8显著降低；在髓质TAL中，PAF使环鸟苷酸含量显著增加了两倍，该作用被PAF拮抗剂BN 50730抑制，而PAF在基础或刺激条件下未显著改变环磷酸腺苷含量。最后，用NAME或NMMA抑制一氧化氮生成未能阻止PAF对氯离子重吸收的作用。得出的结论是，PAF诱导的TAL中氯离子重吸收的抑制作用是由环鸟苷酸介导的，可能独立于一氧化氮合成。
