Interaction of local anaesthetics with recombinant μ, κ, and δ opioid receptors expressed in Chinese hamster ovary cells

K. Hirota, H. Okawa, B. L. Appadu, David Grandy, D. G. Lambert

    Research output: Contribution to journalArticle

    13 Citations (Scopus)

    Abstract

    Local anaesthetics potentiate epidural or intrathecal opioid analgesia via a poorly defined mechanism. In this study, we have examined the interaction of local anaesthetics (lidocaine, bupivacaine and its optical isomers, tetracaine, procaine and prilocaine) with recombinant μ-, κ-, and δ-opioid receptors expressed in Chinese hamster ovary cells (CHO-μ, κ, and δ, respectively). Lidocaine produced a concentration-dependent displacement of radiolabelled opioid antagonist [3H]diprenorphine ([3H]DPN) binding with the following rank order of inhibitor constant (K(i): κ (210 μM) > μ (552 μM) > δ (1810 μM). Procaine, prilocaine, tetracaine and bupivacaine also displaced [3H]DPN binding in CHO- μ with K(i) values of 244, 204, 43 and 161 μM respectively. Lidocaine produced a concentration-dependent and naloxone-insensitive inhibition of cAMP formation in all cell lines including untransfected cells. Concentration producing 50% inhibition of maximum was μ, 1.32 mM; κ, 2.41 mM; δ, 1.27 mM; untransfected, 2.78 mM. When lidocaine (300 μM) was co-incubated with spiradoline (κ-selective) and [D-Ala2, MePhe4, Gly(ol)5] enkephalin (DAMGO μ-selective) in CHO-κ and μ cells we did not observe an additive interaction for cAMP formation. In contrast, there was an apparent inhibitory action of the combination at the κ receptor. This study suggests that clinical concentrations of local anaesthetics interact with μ and κ but not δ opioid receptors. As there was no synergism between local anaesthetics and opioids we suggest that the interaction of these agents in the clinical setting does not occur at the cellular level.

    Original languageEnglish (US)
    Pages (from-to)740-746
    Number of pages7
    JournalBritish Journal of Anaesthesia
    Volume85
    Issue number5
    StatePublished - 2000

    Fingerprint

    Opioid Receptors
    Lidocaine
    Cricetulus
    Local Anesthetics
    Ovary
    Prilocaine
    Tetracaine
    Procaine
    CHO Cells
    Bupivacaine
    Opioid Analgesics
    Diprenorphine
    Ala(2)-MePhe(4)-Gly(5)-enkephalin
    Narcotic Antagonists
    Enkephalins
    Naloxone
    NAD
    Analgesia
    Cell Line

    Keywords

    • Anaesthetics local
    • Measurement techniques, radioligand binding
    • Metabolism, cAMP

    ASJC Scopus subject areas

    • Anesthesiology and Pain Medicine

    Cite this

    Interaction of local anaesthetics with recombinant μ, κ, and δ opioid receptors expressed in Chinese hamster ovary cells. / Hirota, K.; Okawa, H.; Appadu, B. L.; Grandy, David; Lambert, D. G.

    In: British Journal of Anaesthesia, Vol. 85, No. 5, 2000, p. 740-746.

    Research output: Contribution to journalArticle

    Hirota, K. ; Okawa, H. ; Appadu, B. L. ; Grandy, David ; Lambert, D. G. / Interaction of local anaesthetics with recombinant μ, κ, and δ opioid receptors expressed in Chinese hamster ovary cells. In: British Journal of Anaesthesia. 2000 ; Vol. 85, No. 5. pp. 740-746.
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    AU - Lambert, D. G.

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    AB - Local anaesthetics potentiate epidural or intrathecal opioid analgesia via a poorly defined mechanism. In this study, we have examined the interaction of local anaesthetics (lidocaine, bupivacaine and its optical isomers, tetracaine, procaine and prilocaine) with recombinant μ-, κ-, and δ-opioid receptors expressed in Chinese hamster ovary cells (CHO-μ, κ, and δ, respectively). Lidocaine produced a concentration-dependent displacement of radiolabelled opioid antagonist [3H]diprenorphine ([3H]DPN) binding with the following rank order of inhibitor constant (K(i): κ (210 μM) > μ (552 μM) > δ (1810 μM). Procaine, prilocaine, tetracaine and bupivacaine also displaced [3H]DPN binding in CHO- μ with K(i) values of 244, 204, 43 and 161 μM respectively. Lidocaine produced a concentration-dependent and naloxone-insensitive inhibition of cAMP formation in all cell lines including untransfected cells. Concentration producing 50% inhibition of maximum was μ, 1.32 mM; κ, 2.41 mM; δ, 1.27 mM; untransfected, 2.78 mM. When lidocaine (300 μM) was co-incubated with spiradoline (κ-selective) and [D-Ala2, MePhe4, Gly(ol)5] enkephalin (DAMGO μ-selective) in CHO-κ and μ cells we did not observe an additive interaction for cAMP formation. In contrast, there was an apparent inhibitory action of the combination at the κ receptor. This study suggests that clinical concentrations of local anaesthetics interact with μ and κ but not δ opioid receptors. As there was no synergism between local anaesthetics and opioids we suggest that the interaction of these agents in the clinical setting does not occur at the cellular level.

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