Abstract
Intrathecal infusion of the neuropeptide FF analogue, [D-Tyr1, (NMe)Phe3]neuropeptide FF (1DMe; 0.1 microm-0.1 mm) in anaesthetized rats produced a concentration-dependent decrease in the spinal outflow of dynorphin A (1-8)-like material, which persisted for at least 90 min after treatment with 10 microm-0.1 mm of the compound. Co-administration of d-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP; 1 microm) to block spinal micro-opioid receptors did not modify this effect, whereas naltrindole (10 microm) totally prevented it and nor-binaltorphimine (10 microm) reduced the post-effect. These data suggest that 1DMe triggers the release of endogenous opioids that stimulate mainly delta-opioid receptors, and secondarily kappa-opioid receptors, thereby exerting a negative influence on dynorphin A (1-8)-like material outflow. Because dynorphin has pronociceptive properties, such a decrease in spinal dynorphin A (1-8)-like material release might underlie the long-lasting antinociceptive effects of intrathecally administered neuropeptide FF and analogues.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Dose-Response Relationship, Drug
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Dynorphins / cerebrospinal fluid*
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Dynorphins / metabolism
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Injections, Spinal
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Male
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Models, Animal
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Naltrexone / administration & dosage
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Naltrexone / analogs & derivatives*
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Narcotic Antagonists / administration & dosage
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Oligopeptides* / administration & dosage*
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Peptide Fragments / cerebrospinal fluid*
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Peptide Fragments / metabolism
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Perfusion
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Radioimmunoassay
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Rats
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Rats, Sprague-Dawley
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Receptors, Opioid, delta / drug effects
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Receptors, Opioid, kappa / drug effects
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Receptors, Opioid, mu / antagonists & inhibitors
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Somatostatin / administration & dosage
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Somatostatin / analogs & derivatives*
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Spinal Cord / drug effects*
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Spinal Cord / metabolism
Substances
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Narcotic Antagonists
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Oligopeptides
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Peptide Fragments
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Receptors, Opioid, delta
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Receptors, Opioid, kappa
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Receptors, Opioid, mu
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phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide
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tyrosyl-leucyl-N-methylphenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide
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norbinaltorphimine
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Somatostatin
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Naltrexone
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Dynorphins
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dynorphin (1-8)
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phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide
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naltrindole