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• W2188275331 abstract "Dynorphin A(1-17) given intrathecally releases spinal cholecystokinin to produce an antianalgesic action against spinal morphine in the tail-flick test in CD-1 mice. The present study showed that following the cholecystokinin step, a delta(2)-opioid inverse agonist action of Leu-enkephalin (LE), was involved. Pretreatment with intrathecal LE antiserum eliminated dynorphin and cholecystokinin-8s antianalgesia. A small dose of LE intrathecally produced antianalgesia that like that from dynorphin A(1-17) and cholecystokinin was eliminated by naltriben but not 7-benzylidenenaltrexone (delta(2)- and delta(1)-opioid receptor antagonist, respectively). This LE step was followed by N-methyl-D-aspartate (NMDA) receptor activation. MK801, an NMDA receptor antagonist, eliminated the antianalgesia from dynorphin A(1-17), cholecystokinin-8s, and LE. Furthermore, none of the three were effective against morphine analgesia in 129S6/SvEv mice possibly because of their deficiency in NMDA receptor response. In 129S6/SvEv mice, [D-Ser(2)]-Leu-enkephalin-Thr analgesia was not attenuated by LE; thus, this delta(2)-analgesic agonist and LE inverse agonist action did not occur through competition at the same delta(2)-receptor in CD-1 mice. In CD-1 mice, a linear sequence of dynorphin A(1-17) --> cholecystokinin --> LE --> NMDA receptors was indicated: cholecystokinin antiserum inhibited cholecystokinin but not LE; naltriben inhibited LE but not NMDA. The uniqueness of LE in linking dynorphin A(1-17), cholecystokinin, delta(2)-opioid, and NMDA receptor activation may unify the separate known mechanisms involved in the antiopioid actions of these components against morphine." @default.
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• W2188275331 date "2001-05-01" @default.
• W2188275331 modified "2023-09-23" @default.
• W2188275331 title "Inverse agonist action of Leu-enkephalin at delta(2)-opioid receptors mediates spinal antianalgesia." @default.
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