EFFECTS OF POSTNATAL OR ADULT CHRONIC ACETYLCHOLINESTERASE INHIBITION ON MUSCARINIC RECEPTORS, PHOSPHOINOSITIDE TURNOVER AND M(1) MESSENGER-RNA EXPRESSION
EFFECTS OF POSTNATAL OR ADULT CHRONIC ACETYLCHOLINESTERASE INHIBITION ON MUSCARINIC RECEPTORS, PHOSPHOINOSITIDE TURNOVER AND M(1) MESSENGER-RNA EXPRESSION
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DOI：
10.1016/0926-6917(93)90001-7
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发表时间：
1993-12-01
期刊：
影响因子：
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通讯作者：
CATTABENI, F
中科院分区：
文献类型：
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作者：
BALDUINI, W;CIMINO, M;CATTABENI, F
在出生后发育期间或成年时用有机磷二异丙基氟磷酸盐处理大鼠，检测其大脑皮层和海马中的毒蕈碱受体数量、受体刺激的磷酸肌醇水解和m（1）mRNA表达。从出生后第4-9天或出生后第4-20天对发育中的大鼠进行治疗，并分别在第10天和第21天（最后一次给予二异丙基氟磷酸盐后24小时）处死。成年动物给药14天。乙酰胆碱酯酶活性和毒蕈碱受体数量显着减少，在所有治疗组。然而，出生后第4-20天和成年治疗组大鼠的毒蕈碱受体刺激的磷酸肌醇周转率显著降低，但出生后第4-9天组则未降低。未观察到艾德（50）值的差异。相反，在出生后4-9天的治疗大鼠的大脑皮层和海马中，m（1）mRNA的表达显著降低，但在出生后4-20天和成年治疗大鼠中没有。这些结果表明，慢性抑制乙酰胆碱酯酶在发育中的大鼠的结果在毒蕈碱神经传递的显着改变。这些改变可能会延迟胆碱能系统的成熟，因此，可能会解释一些持久的神经毒性作用后观察到的发育暴露于有机磷农药。
Muscarinic receptor number, receptor-stimulated phosphoinositide hydrolysis and m(1) mRNA expression were examined in the cerebral cortex and hippocampus of rats treated during postnatal development or in adult age with the organophosphate diisopropylfluorophosphate. Developing rats were treated from postnatal days 4-9 or from postnatal days 4-20 and killed on days 10 and 21, respectively, 24 h after the last administration of diisopropylfluorophosphate. Adult animals were treated for 14 days. Acetylcholinestarase activity and muscarinic receptor number were significantly reduced in all groups of treatment. Muscarinic receptor-stimulated phosphoinositide turnover, however, was significantly reduced in postnatal days 4-20 and adult treated rats but not in the postnatal days 4-9 group. No differences were observed in ED(50) values. Conversely, m(1) mRNA expression was significantly reduced both in the cerebral cortex and hippocampus of postnatal days 4-9 treated rats, but not of postnatal days 4-20 and adult treated rats. These results indicate that chronic inhibition of acetylcholinesterase in developing rats results in significant alterations in muscarinic neurotransmission. These alterations may delay the maturation of the cholinergic system and, therefore, may account for some of the long-lasting neurotoxic effects observed after developmental exposure to organophosphate pesticides.