Reduction of embryonic intracellular pH: a potential mechanism of acetazolamide-induced limb malformations.
Reduction of embryonic intracellular pH: a potential mechanism of acetazolamide-induced limb malformations.
复制标题
胚胎细胞内 pH 值降低：乙酰唑胺诱导肢体畸形的潜在机制。
DOI：
10.1016/0041-008x(90)90227-l
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发表时间：
1990
影响因子：
3.8
通讯作者：
Collins,MD
中科院分区：
文献类型：
--
作者：
Scott,WJ;Duggan,CA;Schreiner,CM;Collins,MD
假设乙酰唑胺对发育中的啮齿动物肢芽的影响是由于细胞内pH值（pHi）的降低。通过对致畸敏感（c57bl6）和耐药（SWV）近交系小鼠的胎盘分布，计算胚胎细胞内pH。在C57胚胎和肢体芽中，乙酰唑胺处理降低了phih，而在SWV样品中没有。乙酰唑胺致畸可因同时服用阿米洛利而加重，可能是由于后者抑制了Na+H+交换。与单纯乙酰唑胺治疗相比，这种治疗后的ph降低更为显著，进一步支持了中心假设。其他胚胎（胚胎血浆）和胚胎外腔室（外腔液、羊水）的pH值也降低。这些区室的pH值变化也可能导致或促成异常发育。
The effects of acetazolamide on the developing rodent limb bud were postulated to result from a reduction of intracellular pH (pHi). Embryonic intracellular pH was calculated from transplacental distribution of the weak acid, 5,5′-dimethyloxazolidine-2,4-dione, in teratogenically sensitive (C57BL 6 ) and resistant (SWV) inbred mice. pHiwas reduced by acetazolamide treatment in C57 embryos and limb buds but not in SWV samples. Acetazolamide teratogenesis can be exacerbated by coadministration of amiloride, presumably through inhibition of Na+H+exchange attributable to the latter agent. pHireduction after such treatment was more profound than after acetazolamide alone, providing further support for the central hypothesis. pH was also reduced in other embryonic (embryo plasma) and extraembryonic compartments (exocoelomic fluid, amniotic fluid). pH changes in these compartments could also lead or contribute to abnormal development.