RESUMEN
Previously it was demonstrated that nitrous oxide antinociception in the mouse abdominal constriction test is mediated by kappa-opioid receptors. Since nitrous oxide is thought to cause the neuronal release of endogenous opioid peptide to stimulate opioid receptors, this study was designed to identify the opioid peptides involved, especially in the spinal cord, by determining whether nitrous oxide antinociception can be differentially inhibited by intrathecally (i. t.) administered antisera to different opioid peptides. Male NIH Swiss mice were pretreated i.t. with rabbit antisera to opioid peptides then exposed 24 h later to one of three different concentrations of nitrous oxide in oxygen. Dose-response curves constructed from the data indicated that the antinociceptive effect of nitrous oxide was significantly antagonized by antisera to various dynorphins (DYNs) and methionine-enkephalin (ME), but not by antiserum to beta-endorphin (beta-EP). The AD(50) values for nitrous oxide antinociception were significantly elevated by antisera to DYNs and ME but not beta-EP. These findings of this study support the hypothesis that nitrous oxide antinociception in the mouse abdominal constriction test involves the neuronal release of DYN and ME in the spinal cord.
Asunto(s)
Analgésicos no Narcóticos/antagonistas & inhibidores , Sueros Inmunes/inmunología , Sueros Inmunes/farmacología , Óxido Nitroso/antagonistas & inhibidores , Péptidos Opioides/antagonistas & inhibidores , Péptidos Opioides/inmunología , Analgésicos no Narcóticos/farmacología , Analgésicos Opioides/antagonistas & inhibidores , Analgésicos Opioides/inmunología , Analgésicos Opioides/metabolismo , Animales , Relación Dosis-Respuesta a Droga , Dinorfinas/antagonistas & inhibidores , Dinorfinas/inmunología , Dinorfinas/metabolismo , Encefalina Metionina/antagonistas & inhibidores , Encefalina Metionina/inmunología , Encefalina Metionina/metabolismo , Sueros Inmunes/administración & dosificación , Inyecciones Espinales , Masculino , Ratones , Óxido Nitroso/farmacología , Péptidos Opioides/metabolismo , Dolor/metabolismo , Dolor/fisiopatología , Dimensión del Dolor , Fragmentos de Péptidos/antagonistas & inhibidores , Fragmentos de Péptidos/inmunología , Fragmentos de Péptidos/metabolismo , Médula Espinal/efectos de los fármacos , Médula Espinal/metabolismo , Médula Espinal/fisiopatología , betaendorfina/antagonistas & inhibidores , betaendorfina/inmunología , betaendorfina/metabolismoRESUMEN
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.