Mu and delta opioid receptors mediate opposite modulations by morphine of the spinal release of cholecystokinin-like material

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Abstract

The possible modulations by morphine and various opioids of the spinal release of cholecystokinin-like material (CCKLM) evoked by 30 mM K+ was studied in vitro, using slices of the dorsal part of the rat lumbar enlargement superfused with an artificial cerebrospinal fluid. Addition of the μ agonist, DAGO (0.1 - 10 μM), to the perfusing fluid produced a concentration-dependent decrease in the peptide release, which could be prevented by the preferential μ antagonist, naloxone. Complex modulations were induced by the δ agonist, DTLET, as this drug inhibited CCKLM release when added at 10 nM-3 μM to the perfusing fluid, but enhanced it at 10 μM. Both effects were preventable by the δ antagonists naltrindole and ICI 154129, suggesting that δ receptors, possibly of different subtypes, mediated the inhibition and stimulation by DTLET. Morphine also exerted a biphasic effect, as the alkaloid decreased CCKLM release at 0.01 - 0.1 μM and enhanced it at 10 μM. Morphine-induced inhibition was preventable by naloxone, whereas its stimulatory effect could be blocked by naltrindole and ICI 154129. Although inactive on its own on CCKLM release, the selective κ1 agonist U 50488H (1 μM) prevented by the inhibitory effects of both DAGO (10 μM) and morphine (0.1 μM), suggesting the existence of interactions between κ1 and μ receptors within the dorsal zone of the rat spinal cord. These data indicate that low concentrations of morphine exert an inhibitory influence on spinal CCKergic neurons that depends on the stimulation of μ opioid receptors. The excitatory influence of 10 μM morphine likely results from the simultaneous stimulation of μ, δ and κ receptors, as the inhibitory effect of μ receptor stimulation can be masked by that of κ1 receptors, allowing only the expression of a δ-dependent excitatory effect similar to that induced by 10 μM DTLET. © 1994.

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Benoliel, J. J., Collin, E., Mauborgne, A., Bourgoin, S., Legrand, J. C., Hamon, M., & Cesselin, F. (1994). Mu and delta opioid receptors mediate opposite modulations by morphine of the spinal release of cholecystokinin-like material. Brain Research, 653(1–2), 81–91. https://doi.org/10.1016/0006-8993(94)90375-1

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