GLUTAMATE VIA NMDA RECEPTORS PROMOTES THE RELEASE OF NPFF, AN ANTI-OPIOID PEPTIDE, FROM RAT SPINAL-CORD SLICES

Neuropeptide FF (NPFF) is a FMRFamide-like peptide which produces hyperalgesia and inhibits morphine-induced analgesia (1, 2) by acting on its own receptors (3, 4). If NPFF plays a role in the transmission of noxious information, it must fulfil some of the criteria for a neurotransmitter. In this study we showed by superfusion of rat spinal cord slices in vitro, that the NPFF release depends on nerve impulse activity, is sensitive to the extent of depolarization and is calcium-dependent (involvement of P-type Ca2+-channels). Since there is considerable evidence for a role of glutamate in the transmission of nociceptive inputs within the spinal cord, we examined the effects of this substance on NPFF release. Both glutamate and NMDA stimulated NPFF release, which effects were abolished by NMDA receptor antagonists, APV or MK-801. The NMDA-induced release persisted in the presence of the voltage-dependent Na+-channel blocker TTX, suggesting that NMDA receptors are presynaptic. No effect was seen with AMPA or t-ACPD, the quisqualate and metabotropic receptor agonists, respectively. Furthermore, NPFF-like material inhibited [I-125]Y8Fa binding to spinal membranes, suggesting the physiological relevance of NMDA-induced release.