Inhibitive Effect of N-nitro-L-arginine on Hippocampal Neurons Excitation

The inhibitive effect of N-nitro-L-arginine (L-NNA, a nitric oxide synthase inhibitor) on the excitation of cultured rat hippocampal CA1 neurons, stimulated by penicillin G(PG), was investigated. A rapid intracellular NO production induced by PG (4 000 IU/ml) was disclosed when monitored with laser scanningconfocal microscopy (LSCM). Pretreatment of L-NNA (0--10 &mgr;mol/L) dose-dependently inhibited the NO production, and the intercellular level of glutamate (15 min after PG stimulation) as well. Meanwhile, L-NNA(1 and 10 &mgr;mol/L) also significantly inhibited the immunoreactive methionine enkephalin (ir-M-ENK) level. Furthermore, the immunoreactive dynorphin B (ir-DYN-B) level was increased significantly by L-NNA (10 &mgr;mol/L). Finally, beta-FNA (100 &mgr;mol/L, an M-ENK receptor inhibitor) facilitated the inhibitive effect of L-NNA on the Glu level, while nor-BIN (100 &mgr;mol/L, a DYN receptor inhibitor) suppressed that effect. In conclusion,L-NNA could inhibit NO production induced by PG (4 000 IU/ml) stimulation, thuslowering the M-ENK level and increasing the DYN-B level, and resulted in a down-regulation of the Glu level and the neuron excitation.