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• W2070984295 startingPage "664" @default.
• W2070984295 abstract "Opioid receptors in the spinal cord produce strong analgesia, but the mechanisms controlling their activation by endogenous opioids remain unclear. We have previously shown in spinal cord slices that peptidases preclude mu-opioid receptor (MOR) internalization by opioids. Our present goals were to investigate whether enkephalin-induced analgesia is also precluded by peptidases, and whether it is mediated by MORs or delta-opioid receptors (DORs). Tail-flick analgesia and MOR internalization were measured in rats injected intrathecally with Leu-enkephalin and peptidase inhibitors. Without peptidase inhibitors, Leu-enkephalin produced neither analgesia nor MOR internalization at doses up to 100 nmol, whereas with peptidase inhibitors it produced analgesia at 0.3 nmol and MOR internalization at 1 nmol. Leu-enkephalin was 10 times more potent to produce analgesia than to produce MOR internalization, suggesting that DORs were involved. Selective MOR or DOR antagonists completely blocked the analgesia elicited by 0.3 nmol Leu-enkephalin (a dose that produced little MOR internalization), indicating that it involved these two receptors, possibly by an additive or synergistic interaction. The selective MOR agonist endomorphin-2 produced analgesia even in the presence of a DOR antagonist, but at doses substantially higher than Leu-enkephalin. Unlike Leu-enkephalin, endomorphin-2 had the same potencies to induce analgesia and MOR internalization. We concluded that low doses of enkephalins produce analgesia by activating both MORs and DORs. Analgesia can also be produced exclusively by MORs at higher agonist doses. Since peptidases prevent the activation of spinal opioid receptors by enkephalins, the coincident release of opioids and endogenous peptidase inhibitors may be required for analgesia." @default.
• W2070984295 created "2016-06-24" @default.
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• W2070984295 date "2007-10-01" @default.
• W2070984295 modified "2023-10-01" @default.
• W2070984295 title "Comparing analgesia and μ-opioid receptor internalization produced by intrathecal enkephalin: Requirement for peptidase inhibition" @default.
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• W2070984295 doi "https://doi.org/10.1016/j.neuropharm.2007.07.010" @default.
• W2070984295 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2083640" @default.
• W2070984295 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17845806" @default.
• W2070984295 hasPublicationYear "2007" @default.
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