Morizane C, Adachi K, Furutani I, Fujita Y, Akaike A, Kashii S, Honda Y
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Eur J Pharmacol. 1997 Jun 5;328(1):45-9. doi: 10.1016/s0014-2999(97)83026-9.
We investigated whether the inhibition of nitric oxide (NO) synthesis with N(omega)-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of NO synthase, affects N-methyl-D-aspartate (NMDA)-induced neurotoxicity in the rat retina in vivo. A single intravitreal injection of NMDA damaged the ganglion cell layer and the inner plexiform layer without affecting the other retinal layers 7 days after injection. Intravitreal injection of (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5, 10-imine hydrogen maleate (MK-801) with NMDA significantly reduced NMDA-induced degeneration of the retina. NMDA-induced degeneration was also prevented by intravitreal injection of L-NAME but not of D-NAME. The protective effect of L-NAME was antagonized by L-arginine. These results suggest that NO plays an important role in NMDA-induced excitotoxic degeneration in the retina.
我们研究了使用一氧化氮合酶的竞争性抑制剂N（ω）-硝基-L-精氨酸甲酯（L-NAME）抑制一氧化氮（NO）合成是否会影响大鼠视网膜中N-甲基-D-天冬氨酸（NMDA）诱导的体内神经毒性。单次玻璃体内注射NMDA在注射7天后损伤了神经节细胞层和内网状层，而未影响其他视网膜层。与NMDA一起玻璃体内注射（5R，10S）-（+）-5-甲基-10,11-二氢-5H-二苯并[a，d]环庚烯-5,10-亚胺马来酸氢盐（MK-801）可显著减少NMDA诱导的视网膜变性。玻璃体内注射L-NAME可预防NMDA诱导的变性，但注射D-NAME则不能。L-精氨酸可拮抗L-NAME的保护作用。这些结果表明，NO在视网膜中NMDA诱导的兴奋性毒性变性中起重要作用。
