Seifert J, Casida J E
Biochem Pharmacol. 1982 Jun 1;31(11):2065-70. doi: 10.1016/0006-2952(82)90422-1.
Organophosphorus delayed neurotoxicants (phenyl saligenin cyclic phosphate and diisopropyl phosphorofluoridate) altered cyclic AMP (cAMP)-dependent phosphorylation and several other processes in brain homogenates and cytoplasmic microtubules. Phenyl saligenin cyclic phosphate slightly stimulated in vitro cAMP-dependent phosphorylation in brain homogenates of three species (rat, mouse and rabbit) that have been reported to be insensitive to delayed neurotoxicity, whereas it slightly decreased this phosphorylation in brain homogenates of three sensitive species (chicken, cow and pig) and in brain microtubules of chicken and pig. The microtubule-associated processes that were moderately inhibited by phenyl saligenin cyclic phosphate in sensitive species were: in vitro [3H]cAMP binding to protein kinase, in vitro assembly when tubulin rings were absent, and cAMP-dependent phosphorylation of microtubule-associated proteins (MAPs) both in vitro and on intracerebral administration of 32Pi. The endogenous proteases that degrade the high molecular weight MAPs were strongly inhibited in vitro by phenyl saligenin cyclic phosphate and diisopropyl phosphorofluoridate. In contrast, treatment of chickens with diisopropyl phosphorofluoridate remarkably decreased the in vitro stability of their brain cytoplasmic high molecular weight MAPs, perhaps by enhancing the MAPs-degrading protease activity. These findings indicate that the MAPs-protease system is a possible target for organophosphorus delayed neurotoxicants.
有机磷延迟神经毒剂（苯基水杨苷环磷酸酯和氟磷酸二异丙酯）改变了脑匀浆和细胞质微管中环磷酸腺苷（cAMP）依赖性磷酸化及其他几个过程。苯基水杨苷环磷酸酯对三种据报道对延迟神经毒性不敏感的物种（大鼠、小鼠和兔子）的脑匀浆中的体外cAMP依赖性磷酸化有轻微刺激作用，而在三种敏感物种（鸡、牛和猪）的脑匀浆以及鸡和猪的脑微管中，它则轻微降低了这种磷酸化。在敏感物种中，苯基水杨苷环磷酸酯适度抑制的微管相关过程包括：体外[3H]cAMP与蛋白激酶的结合、在无微管蛋白环时的体外组装，以及在体外和脑内注射32Pi时微管相关蛋白（MAPs）的cAMP依赖性磷酸化。降解高分子量MAPs的内源性蛋白酶在体外受到苯基水杨苷环磷酸酯和氟磷酸二异丙酯的强烈抑制。相比之下，用氟磷酸二异丙酯处理鸡显著降低了其脑细胞质高分子量MAPs的体外稳定性，这可能是通过增强MAPs降解蛋白酶的活性实现的。这些发现表明，MAPs - 蛋白酶系统可能是有机磷延迟神经毒剂的作用靶点。
