OPIOID CONTROL OF THE RELEASE OF MET-ENKEPHALIN-LIKE MATERIAL FROM THE RAT SPINAL-CORD

The possible control by opioids of the release of Met-enkephalin-like material (MELM) from the rat spinal cord was investigated in vitro and in vivo. Superfusion of slices of the dorsal zone of the lumbar enlargement with the mu-selective agonists DAGO or PL 017 or the partial selective agonist DTLET produced a significant reduction in the K+-evoked MELM release from these tissues. These effects persisted in the presence ot tetrodotoxin, as expected from their mediation through presynaptically located opioid autoreceptors. Furthermore, the inhibitory effect of DAGO and PL 017, but not that of DTLET, was prevented by the preferential mu-antagonist naloxone. Conversely, the effect of DTLET was prevented by the partial antagonist naltrindole but not by naloxone. In vivo experiments performed in halothane-anaesthetized rats have shown that the intrathecal perfusion of DAGO and DTLET significantly depressed the spontaneous MELM outflow from the whole spinal cord. In contrast to these mu and partial agonists, the kappa-selective agonist U 50488 H did not affect the in vivo- and only slightly reduced (at a very high concentration: 50-mu-M) the in vitro-release of MELM from the rat spinal cord. These data indicate that both mu and partial opioid autoreceptors are involved in a local presynaptic autoinhibitory control of MELM release in the rat dorsal horn.