Guarnieri T, Virgili M, Carraro S, Villani L
Department of Biology, University of Bologna, Italy.
Neurochem Int. 1994 Jun;24(6):559-64. doi: 10.1016/0197-0186(94)90008-6.
The toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, intravitreally injected in goldfish eye, involves interplexiform retinal neurons and depletes tyrosine hydroxylase immunoreactivity and dopamine levels. This induced neurotoxicity was prevented by the concomitant administration in non-toxic doses (10 micrograms) of quinolinic acid, an endogenous structural analogue of N-methyl D-aspartate with excitotoxic properties. Quinolinic acid is ineffective on the retinal degeneration induced by 1-methyl-4-phenylpyridinium ion. This fact suggests that quinolinic acid inhibits the MAO-B oxidation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. MK-801, a noncompetitive antagonist of glutamate NMDA-receptors, exerts partial protective effects on MPTP-induced delayed toxicity in mammals. In the goldfish eye, MK-801, injected in low concentration, and in conjunction with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine or 1-methyl-4-phenylpyridinium ion, did not prevent retinal neurodegeneration. Ten micrograms of MK-801 alone did not affect retinal neurons, while a higher concentration (20 micrograms) causes the chromatolysis of some photoreceptor nuclei.
向金鱼眼玻璃体内注射1-甲基-4-苯基-1,2,3,6-四氢吡啶的毒性作用涉及视网膜网间神经元，并使酪氨酸羟化酶免疫反应性和多巴胺水平降低。通过同时给予无毒剂量（10微克）的喹啉酸（一种具有兴奋性毒性特性的N-甲基-D-天冬氨酸内源性结构类似物）可预防这种诱导的神经毒性。喹啉酸对由1-甲基-4-苯基吡啶离子诱导的视网膜变性无效。这一事实表明，喹啉酸可抑制1-甲基-4-苯基-1,2,3,6-四氢吡啶的单胺氧化酶B氧化。MK-801是一种谷氨酸NMDA受体的非竞争性拮抗剂，对MPTP诱导的哺乳动物延迟毒性具有部分保护作用。在金鱼眼中，低浓度注射的MK-801与1-甲基-4-苯基-1,2,3,6-四氢吡啶或1-甲基-4-苯基吡啶离子联合使用时，并不能预防视网膜神经变性。单独使用10微克的MK-801不会影响视网膜神经元，而较高浓度（20微克）会导致一些光感受器细胞核的染色质溶解。
