Savolainen K M, Hirvonen M R
Department of Pharmacology and Toxicology, University of Kuopio, Finland.
Neurotoxicology. 1992 Spring;13(1):295-9.
Phosphatidylinositol (PI) signaling during organophosphate (OP) induced convulsions and tissue Ca2+ changes in 10 weeks old male, and 14 weeks old non-pregnant and pregnant female rats, and the offspring of the latter were explored. Brain inositol and inositol-1-phosphate (Ins1P) served as indices of alterations in brain PI signaling, and brain tissue Ca2+ as an index of early neuronal injury. A dose of malaoxon OP, which produced convulsions in about 60% of the exposed rats in different rat groups, was 39.2 for male, and 8.2 mg/kg for pregnant female rats, respectively. Malaoxon (8.2 mg/kg) did not produce convulsions in non-pregnant female rats. All the rats were followed for 1 or 4 hr subsequent to malaoxon. Malaoxon decreased cerebral inositol in both male and female rats, and the decrease was similar in spite of the dose difference. The decrease was larger in the convulsing than in the non-convulsing rats. A tendency towards a decrease of brain inositol also occurred in the offspring. Ins1P levels were markedly increased in male, and also in non-pregnant female rats, but not in the brains of pregnant female rats. Ins1P was not markedly changed in the brains of the offspring. Malaoxon elevated brain tissue Ca2+ in male but not in female rats or their offspring. Cholinergic systems and PI signaling in the brain seem to be associated with OP-induced convulsions both in male and female rats; females seem to be more sensitive than males. Malaoxon may also have slightly modified PI signaling in the offspring brain. Hormonal factors are likely to modify OP CNS toxicity and cholinergic stimulation of brain PI signaling.
研究了10周龄雄性大鼠、14周龄未孕和孕龄雌性大鼠及其后代在有机磷（OP）诱导惊厥和组织钙变化过程中的磷脂酰肌醇（PI）信号传导。脑肌醇和肌醇-1-磷酸（Ins1P）作为脑PI信号传导改变的指标，脑组织钙作为早期神经元损伤的指标。导致不同大鼠组中约60%的暴露大鼠惊厥的马拉氧磷OP剂量，雄性大鼠为39.2，孕龄雌性大鼠为8.2mg/kg。马拉氧磷（8.2mg/kg）未使未孕雌性大鼠惊厥。在给予马拉氧磷后，所有大鼠均被观察1或4小时。马拉氧磷降低了雄性和雌性大鼠的脑肌醇，尽管剂量不同，但降低程度相似。惊厥大鼠的降低幅度大于未惊厥大鼠。后代中也出现了脑肌醇降低的趋势。雄性大鼠和未孕雌性大鼠的Ins1P水平显著升高，但孕龄雌性大鼠脑中未升高。后代脑中的Ins1P没有明显变化。马拉氧磷使雄性大鼠脑组织钙升高，但未使雌性大鼠及其后代升高。脑内胆碱能系统和PI信号传导似乎与雄性和雌性大鼠的OP诱导惊厥有关；雌性似乎比雄性更敏感。马拉氧磷也可能对后代脑内的PI信号传导有轻微影响。激素因素可能会改变OP对中枢神经系统的毒性以及脑PI信号传导的胆碱能刺激。
