The neuropeptide FF analogue, 1DMe, reduces in vivo dynorphin release from the rat spinal cord

J Neurochem. 2002 May;81(3):659-62. doi: 10.1046/j.1471-4159.2002.00914.x.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Dynorphins / cerebrospinal fluid*
  • Dynorphins / metabolism
  • Injections, Spinal
  • Male
  • Models, Animal
  • Naltrexone / administration & dosage
  • Naltrexone / analogs & derivatives*
  • Narcotic Antagonists / administration & dosage
  • Oligopeptides* / administration & dosage*
  • Peptide Fragments / cerebrospinal fluid*
  • Peptide Fragments / metabolism
  • Perfusion
  • Radioimmunoassay
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid, delta / drug effects
  • Receptors, Opioid, kappa / drug effects
  • Receptors, Opioid, mu / antagonists & inhibitors
  • Somatostatin / administration & dosage
  • Somatostatin / analogs & derivatives*
  • Spinal Cord / drug effects*
  • Spinal Cord / metabolism

Substances

  • Narcotic Antagonists
  • Oligopeptides
  • Peptide Fragments
  • Receptors, Opioid, delta
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu
  • phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide
  • tyrosyl-leucyl-N-methylphenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide
  • norbinaltorphimine
  • Somatostatin
  • Naltrexone
  • Dynorphins
  • dynorphin (1-8)
  • phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide
  • naltrindole