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Opioid control of the release of Met-enkephalin-like material from the rat spinal cord
S Bourgoin1, E Collin, J J Benoliel
1I.N.S.E.R.M. U.288, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Abstract:
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 delta 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 delta 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 delta agonists, the kappa selective agonist U 50488 H did not affect the in vivo- and only slightly reduced (at a very high concentration: 50 microM) the in vitro-release of MELM from the rat spinal cord. These data indicate that both mu and delta opioid autoreceptors are involved in a local presynaptic autoinhibitory control of MELM release in the rat dorsal horn.
Insights
Opioid receptors, specifically mu and delta types, regulate the release of Met-enkephalin-like material (MELM) in the rat spinal cord. This study reveals a presynaptic autoinhibitory mechanism controlling MELM release in the dorsal horn.
Area of Science:
- Neuroscience
- Pharmacology
- Spinal Cord Research
Background:
- Opioids are known to modulate neurotransmitter release.
- Met-enkephalin-like material (MELM) is an endogenous opioid peptide found in the spinal cord.
- The precise mechanisms of opioid control over MELM release require further elucidation.
Purpose of the Study:
- To investigate the role of opioid receptors in regulating Met-enkephalin-like material (MELM) release from the rat spinal cord.
- To differentiate the involvement of mu, delta, and kappa opioid receptor subtypes in this process.
Main Methods:
- In vitro superfusion of rat spinal cord slices.
- In vivo intrathecal perfusion in anesthetized rats.
- Application of selective mu (DAGO, PL 017), delta (DTLET), and kappa (U 50488 H) opioid agonists.
- Use of opioid antagonists (naloxone, naltrindole) to block receptor activity.
- Measurement of MELM release.
Main Results:
- Mu and delta opioid agonists significantly reduced K(+)-evoked MELM release in vitro and spontaneous MELM outflow in vivo.
- These effects were mediated by presynaptic opioid autoreceptors.
- Naloxone blocked the effects of mu agonists, while naltrindole blocked the effects of the delta agonist.
- Kappa agonists had minimal effect on MELM release.
Conclusions:
- Both mu and delta opioid autoreceptors are involved in the presynaptic autoinhibitory control of MELM release in the rat dorsal horn.
- These findings highlight a localized regulatory mechanism for opioid peptide release in the spinal cord.