A direct chemical interaction between dynorphin and excitatory amino acids.
The endogenous opioid peptide dynorphin A elicits non-opioid receptor-mediated neurotoxic effects. These effects are blocked by pretreatment with N-methyl-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 observed that both glutamate or aspartate bind non-covalently to dynorphin A and dynorphin 2-17. However, when dynorphin A or dynorphin 2-17 were added to an equimolar mixture of Glutamate and Aspartate, they both complexed preferentially with glutamate. These data may explain the non-opioid physiological effects of dynorphin A and related peptides and indicate that the direct chemical interaction between neurotransmitters should be monitored when studying interactions between different neurochemical systems.
Woods
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A
National Institute on Drug Abuse, NIH, Baltimore, MD 21224, USA. awoods@intra.nida.nih.gov
Zangen
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A
D004399:Dynorphins / Q000737:chemistry*; D018846:Excitatory Amino Acids / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D018846:Excitatory Amino Acids; D004399:Dynorphins