Interaction of local anaesthetics with recombinant mu, kappa, and delta-opioid receptors expressed in Chinese hamster ovary cells

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, tet racaine, procaine and prilocaine) with recombinant mu-, kappa-, and F-opioi d receptors expressed in Chinese hamster ovary cells (CHO-mu, kappa, and de lta, respectively). Lidocaine produced a concentration-dependent displaceme nt of radiolabelled opioid antagonist [H-3]diprenorphine ([H-3]DPN) binding with the following rank order of inhibitor constant (Ki): kappa (210 muM) > mu (552 muM) > delta (1810 muM). Procaine, prilocaine, tetracaine and bup ivacaine also displaced [H-3]DPN binding in CHO- mu with K-i values of 244, 204, 43 and 161 muM respectively. Lidocaine produced a concentration-depen dent and naloxone-insensitive inhibition of cAMP formation in all cell line s including untransfected cells. Concentration producing 50% inhibition of maximum was mu, 1.32 mM; kappa-, 2.41 mM; delta, 1.27 mM; untransfected, 2. 78 mM. When lidocaine (300 muM) was co-incubated with spiradoline (kappa -s elective) and [D-Ala(2), MePhe(4), Gly(ol)(5)] enkephalin (DAMGO mu -select ive) in CHO-kappa and mu cells we did not observe an additive interaction f or cAMP formation. In contrast, there was an apparent inhibitory action of the combination at the kappa receptor. This study suggests that clinical co ncentrations of local anaesthetics interact with mu and kappa but not delta opioid receptors. As there was no synergism between local anaesthetics and opioids we suggest that the interaction of these agents in the clinical se tting does not occur at the cellular level.