Effects of high dose of dynorphin on NMDA receptor and NOS activities in spinal cord of rats

OBJECTIVE: To elucidate the effects of N-methyl-D-aspartate(NMDA) receptor and nitric oxide synthase (NOS) activity in dynorphin (Dyn)-induced spinal cord injury. METHODS: The NMDA receptor activity was measured by radio-ligand of 3H-MK801. The constitutive and inducible NOS (cNOS and iNOS) activities were assayed by 3H-arginine conversion. RESULTS: In ventral samples, both 3H-MK801 binding and cNOS activity increased at 0.5 h and persisted for 48 h while iNOS activity enhanced at 4 h after intratheacal injection (i.t.) Dyn A(1-17) at dose of 20 nmol/L. However, the 3H-MK801 binding activity reduced significantly from 4 h to 24 h and cNOS activity did not change at the same time in dorsal samples. 7-nitroindozol (7-NI) and aminoguanidine (AG) inhibited the effects of Dyn A(1-17) (20 nmol/L) on 3H-MK801 binding and NOS activities in ventral samples. N-nitro-L-arginine methyl ester (L-NAME) did not affect the elevation of Dyn A(1-17) on NOS activities but caused 3H-MK801 binding activity reduction in ventral samples. CONCLUSIONS: NMDA-NOS pathway might play important role in Dyn spinal neurotoxicity. NOS inhibitors and Dyn might produce cooperative down-regulation on the function of NMDA-NOS pathway in dorsal cord.