Modulation of neuropeptide FF release from rat spinal cord slices by glutamate. Involvement of NMDA receptors.

This study examined the effects of glutamate receptor agonists on the release of neuropeptide FF-like immunoreactivity from rat spinal dorsal half slices. Glutamate (10 microM) only induced release in Mg(2+)-free medium enriched with glycine (1 microM) and with slight depolarization (15 mM K+). This effect was abolished by the NMDA receptor antagonist, 2-amino-5-phosphonovalerate (100 microM), suggesting major participation of NMDA receptors. The quisqualate and metabotropic receptor agonists, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) and trans-1-hydroxy-5-methylisoxazole-4-propionate (t-ACPD) respectively, had no effect at 10 microM. In contrast, NMDA dose dependently stimulated neuropeptide FF release, even in the presence of the Na+ channel blocker, tetrodotoxin (1 microM), suggesting that NMDA receptors involved in the release of neuropeptide FF are mainly located on nerve terminals. The NMDA receptor antagonists, 2-amino-5-phosphonovalerate or (+)-5-methyl-10-11-dihydro-5H-dibenzo [a,d]cyclohepten-5,10-imine (MK-801) (100 microM), blocked the 10 microM NMDA effect. Furthermore, neuropeptide FF-like material inhibited binding of [125I]Y8Fa, a radioiodinated analog of neuropeptide FF, to spinal membranes, suggesting physiological relevance of NMDA-induced release. Taken together, these results suggest a relationship between neuropeptide FF and NMDA receptors in the spinal cord.