Scott W J, Duggan C A, Schreiner C M, Collins M D
Division of Basic Science Research, Children's Hospital Research Foundation, Cincinnati, Ohio.
Toxicol Appl Pharmacol. 1990 Apr;103(2):238-54. doi: 10.1016/0041-008x(90)90227-l.
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. pHi was 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. pHi reduction 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.
乙酰唑胺对发育中的啮齿动物肢芽的影响被推测是由于细胞内pH值（pHi）降低所致。通过弱酸5,5'-二甲基恶唑烷-2,4-二酮在致畸敏感（C57BL/6）和抗性（SWV）近交系小鼠中的经胎盘分布来计算胚胎细胞内pH值。在C57胚胎和肢芽中，乙酰唑胺处理可降低pHi，但在SWV样本中则不然。乙酰唑胺致畸作用可因联合使用氨氯吡咪而加剧，推测这是由于后者抑制了Na+/H+交换。这种处理后的pHi降低比单独使用乙酰唑胺后更显著，为核心假说提供了进一步支持。在其他胚胎（胚胎血浆）和胚外腔室（卵黄囊液、羊水）中pH值也降低了。这些腔室中的pH值变化也可能导致或促成异常发育。
