Neant F, Bailly C
Laboratoire de Physiologie Rénale, Faculté Xavier Bichat, Université Paris 7, INSERM U 251, France.
Kidney Int. 1993 Oct;44(4):741-6. doi: 10.1038/ki.1993.308.
Since, in the presence of ANF, urinary cGMP was shown to be of glomerular origin, a possible paracrine effect of luminal cGMP on the medullary thick ascending limb (mTAL) function was investigated. Net chloride reabsorption (JCl) was determined on isolated microperfused tubules from mouse kidney. Addition of 10(-6) M cGMP to the lumen significantly decreased JCl by 46.5 +/- 4.6%. A concentration-dependent decrease of the transepithelial voltage was observed, with a 10(-8) M threshold. Added to the bath, ANF (10(-7) M) as well as urodilatin (6 x 10(-8) M) decreased JCl by 29.8 +/- 3.9% and 36.9 +/- 5.1%, respectively, an effect reproduced by 8-bromo cGMP and associated with a significant increase in tubular cGMP content. The inhibitory effect of ANF was similar whether or not cGMP was present in the lumen. Furthermore, increasing intracellular cGMP content by 8-bromo cGMP did not prevent a further effect of luminal cGMP. Finally, H-8, which blocked the effect of ANF, urodilatin, and 8-bromo cGMP, failed to abolish the luminal cGMP-induced decrease of JCl, suggesting that this effect did not require a cGMP-dependent protein kinase activation. It is concluded that luminal cGMP inhibits the reabsorptive function of the mTAL through a pathway different from the intracellular cGMP production.
由于在心房钠尿肽（ANF）存在的情况下，尿中环鸟苷酸（cGMP）显示为肾小球来源，因此研究了管腔cGMP对髓袢升支粗段（mTAL）功能可能的旁分泌作用。在从小鼠肾脏分离的微灌注小管上测定净氯重吸收（JCl）。向管腔中添加10^(-6) M cGMP可使JCl显著降低46.5±4.6%。观察到跨上皮电压呈浓度依赖性降低，阈值为10^(-8) M。添加到浴液中的ANF（10^(-7) M）以及尿舒张素（6×10^(-8) M）分别使JCl降低29.8±3.9%和36.9±5.1%，8-溴cGMP可重现此效应，并伴有小管cGMP含量显著增加。无论管腔中是否存在cGMP，ANF的抑制作用均相似。此外，用8-溴cGMP增加细胞内cGMP含量并不能阻止管腔cGMP的进一步作用。最后，能阻断ANF、尿舒张素和8-溴cGMP作用的H-8未能消除管腔cGMP诱导的JCl降低，这表明该效应不需要cGMP依赖性蛋白激酶激活。结论是管腔cGMP通过不同于细胞内cGMP产生的途径抑制mTAL的重吸收功能。
