Soto C, Del Razo L M, Neri L
Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana-Xochimilco, Calzada del Hueso 1100 Col., Villa Quietud, 04960, Mexico, Mexico.
Comp Biochem Physiol C Toxicol Pharmacol. 2001 Sep;130(1):19-27. doi: 10.1016/s1532-0456(01)00213-7.
Alloxan has been widely used to provoke diabetes mellitus. This compound induces necrosis of the beta-pancreatic cells and the renal tubules. However, the mechanism of this action has not been fully established. There is some evidence that this drug may act by an alteration of several ionic transport mechanisms. Nevertheless, there is scant information on the effect of alloxan on these ionic transport mechanisms of the membrane in epithelial cells. We reported that this drug induces a decrease in sodium transport in the frog skin. In order to obtain information about the mechanism involved in the sodium transport diminution provoked by alloxan, in this study the function of Na+-K+ ATPase enzyme on transepithelial sodium transport altered by alloxan is explored. We measured changes in the short circuit current and in the intracellular content of sodium and potassium under conditions of maximally stimulated enzyme activity. Short circuit current was not modified by the treatment with alloxan during the period of highest activity of the enzyme, suggesting a site of action independent of this ATPase. Cell potassium was reduced in alloxan-treated epithelia, without significant changes in Na+ content. This finding points out the existence of an alteration induced by alloxan of some modulator mechanisms of the intracellular K+ concentration. The treatment of the frog skin with cesium chloride, a K+ channel blocker, prevented the decrease of Na+ transport produced by alloxan. This result suggests an action of this diabetogenic drug on the K+ channels of the frog skin epithelium.
四氧嘧啶已被广泛用于诱发糖尿病。这种化合物会导致胰腺β细胞和肾小管坏死。然而，这种作用机制尚未完全明确。有证据表明，这种药物可能通过改变几种离子转运机制起作用。尽管如此，关于四氧嘧啶对上皮细胞膜这些离子转运机制的影响的信息却很少。我们报道过这种药物会导致蛙皮钠转运减少。为了获得有关四氧嘧啶引起钠转运减少所涉及机制的信息，在本研究中，我们探究了四氧嘧啶改变的跨上皮钠转运中Na+-K+ATP酶的功能。我们在酶活性受到最大刺激的条件下，测量了短路电流以及细胞内钠和钾含量的变化。在酶活性最高的时期，用四氧嘧啶处理并未改变短路电流，这表明其作用位点与该ATP酶无关。用四氧嘧啶处理的上皮细胞中的细胞内钾减少，而钠含量没有显著变化。这一发现指出四氧嘧啶诱导了细胞内钾浓度的某些调节机制发生改变。用钾通道阻滞剂氯化铯处理蛙皮，可防止四氧嘧啶引起的钠转运减少。这一结果表明这种致糖尿病药物对蛙皮上皮细胞的钾通道有作用。
