INDUCTION OF NEW CARBONIC ANHYDRASE-II FOLLOWING TREATMENT WITH ACETAZOLAMIDE IN DBA AND C57 MICE
INDUCTION OF NEW CARBONIC ANHYDRASE-II FOLLOWING TREATMENT WITH ACETAZOLAMIDE IN DBA AND C57 MICE
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DOI：
10.1111/j.1528-1157.1986.tb03576.x
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发表时间：
1986-09-01
期刊：
影响因子：
5.6
通讯作者：
WOODBURY, DM
中科院分区：
文献类型：
--
作者：
BANKS, DA;ANDERSON, RE;WOODBURY, DM
采用定量免疫细胞化学方法探讨了动物对碳酸酐酶（CA）抑制剂乙酰唑胺抗癫痫作用产生耐受的机制。在对照组和乙酰唑胺（40和200 mg/kg）治疗1、3和5天后，用抗小鼠CA II抗体对听源性癫痫发作敏感的DBA/2 J小鼠和不敏感的C57 BL/6 J小鼠的大脑皮质切片进行染色。在CA II荧光强度的百分比增加，从C57小鼠用40和200毫克/公斤乙酰唑胺治疗的那些未处理的小鼠的细胞分别为22和36%，分别在1天后，32和40%，分别在3天后，和17和40%，分别在5天后的治疗。与对照组相比，DBA小鼠细胞荧光强度的相应百分比增加在治疗1天后分别为13和32%，在治疗3天后分别为17和41%，在治疗5天后分别为26和58%。来自未处理的DBA小鼠的细胞的荧光强度比未处理的C57小鼠的荧光强度大35%。在C57小鼠中，每个剂量下每个细胞的CA II最大量发生在乙酰唑胺治疗后24小时，而DBA小鼠中的CA II量随时间和剂量持续增加至5天。这两种菌株之间的差异可以解释为CA II的亚细胞位置分布的变化或分子磷酸化的缺陷。
The mechanism by which animals develop tolerance to the antiepileptic effects of the carbonic anhydrase (CA) inhibitor, acetazolamide, was explored using a quantitative immunocytochemical method. Cerebral cortex sections of DBA/2J mice susceptible to audiogenic seizures and of C57BL/6J nonsusceptible mice were stained with antibody to mouse CA II in controls and following treatment with acetzolamide (40 and 200 mg/kg) for 1, 3, and 5 days. The percentage increases in CA II fluorescent intensity of cells from C57 mice treated with 40 and 200 mg/kg acetazolamide over those of untreated mice were 22 and 36%, respectively, after 1 day, 32 and 40%, respectively, after 3 days, and 17 and 40%, respectively, after 5 days of treatment. The corresponding percentage increases in fluorescent intensity of cells from DBA mice over controls were 13 and 32%, respectively, after 1 day, 17 and 41%, respectively, after 3 days, and 26 and 58%, respectively, after 5 days of treatment. The fluorescent intensity of cells from untreated DBA mice was 35% greater than those of untreated C57 mice. In C57 mice the maximum amount of CA II per cell at each dose occurred 24 h after acetazolamide treatment, whereas the amount in DBA mice continued to increase with time and dose up to 5 days. The differences between the two strains can be explained by changes in distribution of CA II to subcellular locations or by defects in phosphorylation of the molecule.