Abstract

In superfusion experiments in vitro, facilitation of naloxone-releasable morphine was observed with slices of corpus striatum which were obtained from mice pretreated in vivo with leucine enkephalin (20 mg/kg) i.p. 15 min prior to killing. Preincubation of striatal slices for 15 min with leucine enkephalin in vitro at concentrations ranging from 1.0 nM to 0.1 pM also enhanced the morphine-releasing effect of naloxone. Thus, very minute concentrations of leucine enkephalin are required to produce this effect. Methionine enkephalin pretreatment either in vivo or in vitro did not exhibit any of the above effects. Simultaneous incubation of an equimolar concentration of naloxone blocked this enhancing effect of leucine enkephalin. Prior incubation with leucine enkephalin did not influence naltrexone-releasable [³H]naltrexone but markedly enhanced morphine-releasable [³H]naltrexone and morphine- or levorphanol-releasable [³H]morphine. We suggest that the apparent increase in naloxone potency is mediated by narcotic agonists and that leucine enkephalin potentiates this agonistic effect via a receptor-mediated process. Similar effects of leucine enkephalin on the narcotic-induced enhancement of naloxone potency were observed in vivo. These data also indicate a possible modulatory effect of leucine enkephalin on the opioid receptor.