A direct chemical interaction between dynorphin and excitatory amino acids

The endogenous opioid peptide dynorphin A elicits non-opioid receptor-media ted neurotoxic effects. These effects are blocked by pretreatment with N-me thyl-D-aspartate (NMDA) receptor antagonists. Herein, the mechanism for the non-opioid effects of dynorphin and related peptides was studied by matrix -assisted laser desorption ionization (MALDI) mass-spectrometry. We observe d that both glutamate or aspartate bind non-covalently to dynorphin A and d ynorphin 2-17. However, when dynorphin A or dynorphin 2-17 were added to an equimolar mixture of Glutamate and Aspartate, they both complexed preferen tially with glutamate. These data may explain the non-opioid physiological effects of dynorphin A and related peptides and indicate that the direct ch emical interaction between neurotransmitters should be monitored when study ing interactions between different neurochemical systems.