Hirvonen M R, Savolainen K M
Division of Environmental Health, National Public Health Institute, Kuopio, Finland.
Hum Exp Toxicol. 1993 Nov;12(6):469-77. doi: 10.1177/096032719301200604.
Alterations in malaoxon-(MO)-induced brain regional phosphoinositide (PI) turnover and in brain calcium levels were studied in female non-pregnant and pregnant rats, and in their offspring. The adult rats were followed for 1 or 4 h after MO for tonic-clonic convulsions. A dose of 8.2 mg kg-1 of MO caused similar convulsions in 74% of the pregnant rats as we have reported in young male rats with a dose of 39.2 mg kg-1. However, convulsions did not occur in non-pregnant female rats. Inositol and inositol monophosphate levels were similar in all control rats. MO decreased brain inositol both in pregnant and non-pregnant female rats, and in the cerebellum of the offspring. In contrast to the findings in male rats, MO only randomly increased brain inositol-1-phosphate in female rats, or in their offspring. However, cerebral inositol-4-phosphate levels were similarly increased both in the non-pregnant and the pregnant rats irrespectively of convulsions. MO did not elevate cerebral Ca2+ in female rats or their offspring, in contrast to the male rats. The present results suggest that female rats are more sensitive than male rats to MO-induced PI signalling, and during pregnancy, also to MO-induced overt convulsions, but not to changes in cerebral Ca2+.
在未怀孕和怀孕的雌性大鼠及其后代中,研究了马拉氧磷(MO)诱导的脑区磷酸肌醇(PI)代谢变化和脑钙水平。成年大鼠在给予MO后观察1或4小时,以观察强直性阵挛性惊厥情况。8.2毫克/千克的MO剂量在74%的怀孕大鼠中引起了类似的惊厥,这与我们报道的给予39.2毫克/千克剂量的年轻雄性大鼠的情况相似。然而,未怀孕的雌性大鼠未发生惊厥。所有对照大鼠的肌醇和肌醇单磷酸水平相似。MO降低了怀孕和未怀孕雌性大鼠以及后代小脑的脑肌醇水平。与雄性大鼠的研究结果相反,MO仅随机增加雌性大鼠或其后代的脑肌醇-1-磷酸水平。然而,无论是否发生惊厥,未怀孕和怀孕大鼠的脑肌醇-4-磷酸水平均同样升高。与雄性大鼠不同,MO并未升高雌性大鼠及其后代的脑Ca2+水平。目前的结果表明,雌性大鼠比雄性大鼠对MO诱导的PI信号更敏感,并且在怀孕期间,对MO诱导的明显惊厥也更敏感,但对脑Ca2+的变化不敏感。