U-50,488H inhibits dynorphin and glutamate release from guinea pig hippocampal mossy fiber terminals.
The selective kappa opioid agonist U-50,488H was tested for its ability to modulate the potassium-induced rise of cytosolic Ca2+ in, and transmitter release from, guinea pig hippocampal mossy fiber synaptosomes. U-50,488H dose dependently inhibited the potassium-induced rise in synaptosomal free Ca2+ levels. This inhibition was attenuated by the selective kappa opioid antagonist nor-binaltorphimine, but was insensitive to naloxone and the sigma opioid antagonist ICI 174,864. U-50,488H also dose dependently depressed the potassium-induced release of L-glutamate and dynorphin B-like immunoreactivity from mossy fiber synaptosomes in a nor-binaltorphimine-sensitive manner. This is the first report to confirm the presence of a presynaptic kappa opioid receptor in the hippocampal mossy fiber-CA3 synapse and the nature of its influence on neurotransmitter release. The present results may be used to suggest that endogenous dynorphin peptides interact with this kappa opioid receptor to autoregulate the excitatory mossy fiber synaptic input.
Department of Anatomy and Cell Biology, School of Medicine, East Carolina University, Greenville, NC 27858.
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Gannon
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Terrian
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004399:Dynorphins / Q000378:metabolism*; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D005971:Glutamates / Q000378:metabolism*; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009411:Nerve Endings / Q000187:drug effects / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects / Q000502:physiology*
D000700:Analgesics; D005971:Glutamates; D009292:Narcotic Antagonists; D011759:Pyrrolidines; D009270:Naloxone; C051844:norbinaltorphimine; D004743:Enkephalin, Leucine; D009271:Naltrexone; D011189:Potassium Chloride; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D004399:Dynorphins; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine; D002118:Calcium