Shimizu T, Nakamura M, Yoshitomi K, Imai M
Shionogi Research Laboratories, Osaka, Japan.
Am J Physiol. 1991 Jul;261(1 Pt 2):F36-43. doi: 10.1152/ajprenal.1991.261.1.F36.
To determine the renal tubular site and mechanism of the anticalciuric effects of trichloromethiazide (TCM) and amiloride, we studied the effects of these diuretics on net Ca2+ absorption (JCa) in isolated rabbit connecting tubules (CNT) and cortical collecting ducts (CCD). TCM (100 microM) in the lumen increased JCa in the CNT without affecting lumen-negative transepithelial voltage (VT). This effect was dependent on the amount of parathyroid hormone (PTH, 0.1 or 1 nM) in the bath. TCM had no detectable effect on JCa in the absence of PTH. Addition of 100 microM ouabain to the bath decreased PTH-stimulated JCa and abolished the TCM-stimulated JCa. Elimination of Na+ from the lumen increased PTH-stimulated JCa. Under this condition the ability of TCM to increase JCa was abolished, suggesting that the inhibition of Na+ entry from the lumen with TCM may account for the increase in PTH-stimulated JCa. Elimination of Na+ from the bath in the presence of PTH decreased JCa and abolished the stimulatory effect of TCM on JCa in the presence of PTH. Changes in VT caused by amiloride may not account for the increase in JCa, because JCa was not changed when VT was deflected to more positive direction by increasing bath K+ from 5 to 15 mM. Neither TCM nor amiloride affected JCa in the CCD. From these observations, we speculate that the inhibition of Na+ entry across the apical cell membrane by either thiazides or amiloride may stimulate PTH-induced JCa. The intact Na(+)-Ca2+ antiporter in the basolateral cell membrane is essential for the anticalciuric effect of thiazides and amiloride.
为了确定三氯噻嗪（TCM）和阿米洛利的抗钙尿作用的肾小管部位及机制，我们研究了这些利尿剂对离体兔连接小管（CNT）和皮质集合管（CCD）中净Ca2+吸收（JCa）的影响。管腔内的TCM（100 microM）增加了CNT中的JCa，而不影响管腔负跨上皮电压（VT）。这种作用依赖于浴液中甲状旁腺激素（PTH，0.1或1 nM）的量。在没有PTH的情况下，TCM对JCa没有可检测到的作用。向浴液中添加100 microM哇巴因可降低PTH刺激的JCa，并消除TCM刺激的JCa。从管腔中去除Na+可增加PTH刺激的JCa。在这种情况下，TCM增加JCa的能力被消除，这表明TCM抑制管腔中Na+的进入可能是PTH刺激的JCa增加的原因。在存在PTH的情况下从浴液中去除Na+会降低JCa，并消除TCM在存在PTH时对JCa的刺激作用。阿米洛利引起的VT变化可能无法解释JCa的增加，因为当通过将浴液K+从5 mM增加到15 mM使VT向更正的方向偏移时，JCa没有改变。TCM和阿米洛利对CCD中的JCa均无影响。基于这些观察结果，我们推测噻嗪类或阿米洛利抑制Na+跨顶端细胞膜的进入可能会刺激PTH诱导的JCa。基底外侧细胞膜中完整的Na(+)-Ca2+反向转运蛋白对于噻嗪类和阿米洛利的抗钙尿作用至关重要。
