Abstract: Intrathecal (I. T.)administration of K opioid dynorphin A (1-17) is used as a model of neurological dysfunction which lnvolved in spinal cord injury and secondary affection according to several previous reports. 5-amlno-2-phosphoveroleric acid (APV ), an NMDA receptor antagonist, can significantlly prevent the hindlimb paralysis in rats produced by I. T. dynorPhin A (1-17). To further investigate the mechanisms, we establis11 a nlodel of [³H]L,-Glu release in rats spinal slices influenced by dynorphin A (dynA ) (1-17). [³H]L-Glu release evoked by high [K⁺] (5Ommol/L,)is a Ca²⁺-dependent process. DynA (1-17) slgnificantly inhibited [³H]L,-Glu release at 1O^-8mol/L,, but very significantly enhanced [³H]L-Glu release at 10^-6 mol /L. The synthetic k agonist U50, 488H, which has no neurotoxic effect, inhibited [³H]L-Glu release at both high and low concentrations and did not have any enhancing effect. The results suggest that the analgesic effect of dynA (1-17) at physiological dosage may be rnediated by presynaptic K opioid receptor through the inhibition of Ca²⁺ influx and L-Glu release;but dynA (1-l7)enhanced L-Glu release through a non-opioid pathway and induced hindlimb paralysis at high neurotoxic dosage.

Key words: spinal cord injury, dynorphin, glutamate release, NMDA receptor