1,2-Dimethylhydrazine-induced alterations in Na+-H+ exchange in rat colonic brush-border membrane vesicles.
1,2-Dimethylhydrazine-induced alterations in Na+-H+ exchange in rat colonic brush-border membrane vesicles.
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DOI：
10.1016/0005-2736(88)90146-0
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发表时间：
1988-03
期刊：
影响因子：
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通讯作者：
T. Brasitus;P. Dudeja;E. S. Foster
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文献类型：
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作者：
T. Brasitus;P. Dudeja;E. S. Foster
每周皮下 (sc) 剂量为 20 毫克/公斤体重的二甲肼，几乎 100% 的啮齿动物都会产生结肠肿瘤，潜伏期约为 6 个月。为了确定在二甲基肼诱导的结肠癌发生之前是否存在Na+-H+交换的改变，给大鼠皮下注射该试剂（每周20毫克/千克体重）或稀释剂5周。然后处死动物，制备大鼠结肠刷状缘膜囊泡，测量阿米洛利敏感的钠刺激质子流出，并在对照和治疗制剂中进行比较。这些研究的结果表明，二甲基肼处理：(1)利用荧光pH敏感染料吖啶橙，显着增加了该交换的V max ，而没有改变该交换过程中钠的K m ； 22 Na通量实验还表明，经过处理的膜囊泡的阿米洛利敏感的质子刺激的钠流入增加；（2）与对照制剂相比，似乎没有显着影响处理制剂中的Na+渗透性或质子传导性；（3）使用吖啶橙，没有显着影响肾皮质刷状缘膜囊泡中阿米洛利敏感的钠刺激的质子流出的动力学参数。因此，该数据表明，大鼠结肠刷状缘膜中Na+-H+交换的改变可能参与了该致癌物在大肠中诱导的恶性转化过程。
Dimethylhydrazine in weekly subcutaneous (sc) doses of 20 mg/kg weight, produces colonic tumors in virtually 100% of rodents, with a latency period of approximately 6 months. To determine whether alterations in Na+—H+ exchange existed before the development of dimethylhydrazine-induced colon cancer, rats were given sc injections of this agent (20 mg/kg body wt. per week) or diluent for 5 weeks. Animals were then killed, rat colonic brush-border membrane vesicles prepared and amiloride-sensitive sodium-stimulated proton efflux was measured and compared in control and treated-preparations. The results of these studies demonstrated that dimethylhydrazine treatment:(1) significantly increased the V max of this exchange without altering the K m for sodium of this exchange process, utilizing the fluorescent pH-sensitive dye, acridine orange; 22 Na flux experiments also demonstrated an increase in amiloride-sensitive proton-stimulated sodium influx across treated-membrane vesicles;(2) did not appear to significantly influence Na+ permeability or proton conductance in treated-preparations compared to their control counterparts;(3) did not significantly affect the kinetic parameters of amiloride-sensitive sodium-stimulated proton efflux in renal cortex brush-border membrane vesicles using acridine orange. This data, therefore, suggests that alterations in Na+—H+ exchange in rat colonic brush-border membranes may be involved in the malignant transformation process induced by this procarcinogen in the large intestine.