Warnock D G, Yang W C, Huang Z Q, Cragoe E J
Department of Medicine, Veterans Administration Medical Center, San Francisco, California 94121.
J Biol Chem. 1988 May 25;263(15):7216-21.
Amiloride is a reversible inhibitor of the Na+/H+ antiporter which acts at the external aspect of the transport system. The kinetics of inhibition of the Na+/H+ antiporter with amiloride have been controversial, with the usual finding of simple competitive inhibition, but with other reports of mixed and noncompetitive inhibition of the transporter by amiloride. The present experiments demonstrate that the chloride content of the external transport buffer affects the kinetics of amiloride inhibition. Either simple competitive or mixed inhibition by amiloride was observed in the same vesicle preparations depending on the presence of chloride or gluconate in the buffer. The effect of chloride on the inhibitory effect of amiloride was dependent on the concentration of chloride and amiloride. Similar effects were observed with more potent analogues of amiloride. These findings suggest that the external aspect of the antiporter has a site or sites at which the inhibitory effects of amiloride on the Na+/H+ antiporter can be modified by chloride, even though chloride has only slight effects on the kinetics of the Na+/H+ antiporter in the absence of amiloride.
氨氯吡咪是一种可逆的Na⁺/H⁺反向转运体抑制剂，作用于转运系统的外部。氨氯吡咪对Na⁺/H⁺反向转运体的抑制动力学一直存在争议，通常发现为简单竞争性抑制，但也有其他报道称氨氯吡咪对该转运体有混合性和非竞争性抑制作用。目前的实验表明，外部转运缓冲液中的氯离子含量会影响氨氯吡咪抑制的动力学。根据缓冲液中氯离子或葡萄糖酸盐的存在情况，在相同的囊泡制剂中观察到氨氯吡咪的简单竞争性或混合性抑制。氯离子对氨氯吡咪抑制作用的影响取决于氯离子和氨氯吡咪的浓度。用更有效的氨氯吡咪类似物也观察到了类似的效果。这些发现表明，即使在没有氨氯吡咪的情况下氯离子对Na⁺/H⁺反向转运体的动力学只有轻微影响，但反向转运体的外部有一个或多个位点，在这些位点上氨氯吡咪对Na⁺/H⁺反向转运体的抑制作用可被氯离子改变。
