Role of brain dynorphin in nitrous oxide antinociception in mice.
Earlier studies indicate that nitrous oxide antinociception is mediated by opioid receptors, and we have hypothesized that nitrous oxide stimulates a neuronal release of an endogenous opioid peptide (EOP) that stimulates opioid receptors. To further test this hypothesis, male NIH Swiss mice were pretreated intracerebroventricularly with rabbit antisera to opioid peptides or with various inhibitors of peptidases involved in the degradation of EOPs. Mice were subsequently exposed to three different concentrations of nitrous oxide in oxygen, and their antinociceptive responsiveness was measured using the acetic acid abdominal constriction test. Nitrous oxide antinociception was significantly attenuated by 24-h pretreatment with antisera to various fragments of dynorphin (DYN) but not by antisera against methionine-enkephalin (ME) or beta-endorphin (beta-EP). In other experiments, nitrous oxide antinociception was significantly enhanced by 30-min pretreatment with phosphoramidon, an inhibitor of endopeptidase 24.11, which has been implicated in DYN degradation, but not bestatin or captopril, which inhibit aminopeptidase and angiotensin-converting enzyme, respectively. The latter enzymes have been implicated in degradation of certain EOPs albeit not DYN. These findings support the hypothesis that nitrous oxide antinociception in the mouse abdominal constriction test is mediated by endogenous DYN acting in the central nervous system.
Branda
E M
EM
Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, 61107, USA.
Ramza
J T
JT
Cahill
F J
FJ
Tseng
L F
LF
Quock
R M
RM
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins / Q000037:antagonists & inhibitors / Q000502:physiology*; D006020:Glycopeptides / Q000494:pharmacology*; D007106:Immune Sera / Q000494:pharmacology; D008297:Male; D051379:Mice; D009609:Nitrous Oxide / Q000494:pharmacology*; D018847:Opioid Peptides / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects*; D011480:Protease Inhibitors / Q000494:pharmacology*; D011817:Rabbits
D000700:Analgesics; D006020:Glycopeptides; D007106:Immune Sera; D018847:Opioid Peptides; D011480:Protease Inhibitors; D004399:Dynorphins; D009609:Nitrous Oxide; C008890:phosphoramidon