A novel interaction between dynorphin(1–13) and an [formula omitted] site

Abstract

Dynorphin injected intrathecally in the rat results in a neurotoxicity behaviorally expressed as an irreversible loss of the thermally evoked tail-flick. The excitatory amino acid antagonists dl-2-amino-5-phosphonovalerate (APV) and γ- d-glutamylglycine (DGG) blocked the loss of the tail-flick reflex. The order of potency (APV > DGG) suggests that the N- methyl- d-aspartate (NMDA) subclass of excitatory amino acid receptors participate in the neurotoxicity. Additionally, intrathecal injection of APV results in a reversible loss of the tail-flick reflex, whereas with DGG doses which block the tail-flick reflex also result in hindlimb paralysis. These data suggest that neurotransmission in the tail-flick reflex pathway is, in part, mediated by NMDA receptors. From these and previous findings it was concluded that dynorphin neurotoxicity resuls from enhanced, excitotoxic, transmission across these synapses utilizing NMDA receptors.