naltrindole and dynorphin-(1-8)

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.

Topics: Animals; Dose-Response Relationship, Drug; Dynorphins; Injections, Spinal; Male; Models, Animal; Naltrexone; Narcotic Antagonists; Oligopeptides; Peptide Fragments; Perfusion; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Receptors, Opioid, delta; Receptors, Opioid, kappa; Receptors, Opioid, mu; Somatostatin; Spinal Cord