Endogenous dynorphin modulates calcium-mediated antinociception in mice.
We previously reported that calcium administered IT produces antinociception by stimulating spinal Met-enkephalin release. However, at times the antinociceptive effects of calcium in the tail-flick test are greatly diminished. The results of this study indicates that during these periods calcium also stimulates endogenous dynorphin release. Dynorphin has been reported to block opiate-induced antinociception. Calcium-injected mice (150-600 nmol, IT) pretreated with vehicle IP displayed a poor degree of antinociception. Alternatively, pretreating mice with pentobarbital (45 mg/kg, IP) restored the antinociceptive effects of calcium. Low doses of naloxone and norbinaltorphimine (BNI) did not produce antinociception but restored the antinociceptive effects of calcium. Dynorphin (1-17) (Dyn 1-17), and Dyn (1-13), but not Dyn (1-8), blocked the antinociceptive effects of calcium restored with pentobarbital. These results indicate that calcium-mediated antinociception was sensitive to injected dynorphins. In additional experiments, antiserum to Dyn (1-13) was found to restore the antinociceptive effects of calcium, presumably by binding dynorphin released by calcium.
Smith
F L
FL
Department of Pharmacology and Toxicology, Virginia Commonwealth University/Medical College of Virginia, Richmond 23298-0613.
Dewey
W L
WL
D000818:Animals; D002118:Calcium / Q000008:administration & dosage / Q000494:pharmacology*; D004399:Dynorphins / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology
D010446:Peptide Fragments; D009270:Naloxone; C051844:norbinaltorphimine; D009271:Naltrexone; C026843:dynorphin (1-13); D004399:Dynorphins; C026770:dynorphin (1-8); D002118:Calcium; D010634:Phenobarbital