关于氨苯蝶啶的作用机制：对Na⁺、K⁺和H⁺/HCO₃⁻离子转运的影响

On the mechanism of action of triamterene: effects on transport of Na+, K+, and H+/HCO3- -ions.

作者信息

Knauf H, Wais U, Lübcke R, Albiez G

出版信息

Eur J Clin Invest. 1976 Jan 30;6(1):43-50. doi: 10.1111/j.1365-2362.1976.tb00492.x.

DOI:10.1111/j.1365-2362.1976.tb00492.x

Abstract

The rat salivary duct epithelium, which actively transports Na+, K+, and H+/HCO3- in a manner similar to renal distal tubules, was used as a model tissue to study the mechanism of action of triamterene on electrolyte transport. 10(-4) M triamterene completely blocked Na+ resorption and lowered net K+ secretion to half that of controls, whereas HCO3- accumlated in the lumen, probably due to a decrease in H+ secretion. The rates of K+ and H+/HCO3- transport in the presence of triamterene did not differ from those determined after omission of Na+ from the luminal fluid. This was considered to be evidence against a direct action of triamterene on transport of K+ and H+/HCO3-. Triamterene rapidly and reversibly reduced the transepithelial electrical potential difference. This was due to almost complete abolition of Na+ conductance of the luminal membrane at 10(-4) M triamterene, whereas K+ conductance was not altered. Triamterene, administered in vitro from the interstitial side of the isolated duct epithelium was ineffective even at the highest concentrations. The activities of the Na-K-ATPase, the Mg-ATPase and the microsomal HCO3-ATPase were influenced by 10(-4) M triameterene in a similiar fashion. These effects were clearly demonstrated only in the homogenate of the duct tissue and not in intact cells in the isolated duct preparation. Therefore they were considered unspecific. The transport studied demonstrate a primary effect of triamterene on Na+ entry from lumen to cell. Influences on net K+ and H+/HCO3 transport are secondary consequences of functional coupling between movement of Na+ and movement of K+ and H+ across the luminal cell membrane.

摘要

大鼠唾液腺导管上皮细胞以类似于肾远端小管的方式主动转运Na⁺、K⁺和H⁺/HCO₃⁻，被用作模型组织来研究氨苯蝶啶对电解质转运的作用机制。10⁻⁴M氨苯蝶啶完全阻断Na⁺重吸收，并使净K⁺分泌降至对照组的一半，而HCO₃⁻在管腔内蓄积，这可能是由于H⁺分泌减少所致。在氨苯蝶啶存在的情况下，K⁺和H⁺/HCO₃⁻的转运速率与从管腔液中去除Na⁺后测定的速率没有差异。这被认为是反对氨苯蝶啶对K⁺和H⁺/HCO₃⁻转运有直接作用的证据。氨苯蝶啶迅速且可逆地降低跨上皮电位差。这是由于在10⁻⁴M氨苯蝶啶时管腔膜的Na⁺电导几乎完全消失，而K⁺电导未改变。从分离的导管上皮细胞的间质侧体外给予氨苯蝶啶，即使在最高浓度下也无效。Na⁺-K⁺-ATP酶、Mg-ATP酶和微粒体HCO₃⁻-ATP酶的活性受到10⁻⁴M氨苯蝶啶的类似影响。这些作用仅在导管组织的匀浆中明显表现出来，而在分离的导管制剂中的完整细胞中未表现出来。因此，它们被认为是非特异性的。所研究的转运表明氨苯蝶啶对Na⁺从管腔进入细胞有主要作用。对净K⁺和H⁺/HCO₃⁻转运的影响是Na⁺运动与K⁺和H⁺跨管腔细胞膜运动之间功能偶联的次要结果。