Dynorphin increases extracellular levels of excitatory amino acids in the brain through a non-opioid mechanism.
Administration of dynorphin A-(1-17) (Dyn 1-17), through a microdialysis probe stereotaxically placed into rat hippocampus, caused marked increases in the extracellular levels of glutamate and aspartate. The degree and duration of elevation of these excitatory amino acids (EAA) induced by Dyn 1-17 were dose dependent but were not modified by the centrally active opioid receptor antagonist nalmefene. At comparable doses, Dyn 2-17, which is inactive at the opioid receptor, produced similar alterations in EAA as Dyn 1-17, whereas Dyn 1-8 caused significantly smaller changes of glutamate. Dynorphin and EAAs have each been implicated as pathophysiological factors in brain or spinal cord injuries, with dynorphin's actions shown to involve both opioid and non-opioid components. The present observations indicate a direct potential linkage between dynorphin and excitotoxin mechanisms of CNS injury and provide further support for the concept that dynorphin's pathophysiologic effects may include non-opioid actions of this peptide.
Faden
A I
AI
Department of Neurology, Georgetown University School of Medicine, Washington, D.C. 20007.
D000409:Alanine / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003956:Dialysis / Q000379:methods; D004399:Dynorphins / Q000008:administration & dosage / Q000494:pharmacology*; D005971:Glutamates / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D007700:Kinetics; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012694:Serine / Q000378:metabolism; D013238:Stereotaxic Techniques; D013654:Taurine / Q000378:metabolism; D013912:Threonine / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000596:Amino Acids; D005971:Glutamates; D018377:Neurotransmitter Agents; D010446:Peptide Fragments; D005973:Glutamine; D013654:Taurine; D013912:Threonine; D001224:Aspartic Acid; D012694:Serine; D005680:gamma-Aminobutyric Acid; D004399:Dynorphins; C026770:dynorphin (1-8); D000409:Alanine; D005998:Glycine