European journal of pharmacology
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The local anaesthetic bupivacaine has recently been proposed to inhibit Na+ channels indirectly by making the resting potential less negative. To test this hypothesis we analysed the effects of bupivacaine on voltage and current clamped nodes of Ranvier. Contrary to the hypothesis, the leak current and the resting potential were unaffected. ⋯ The effect on the Na+ current was tentatively explained by a single-site, state-dependent binding model (Kd = 44 microM), while that on the K+ current was explained by two population-specific mechanisms, one open-state dependent (Kd = 550 microM) and one state independent (Kd = 59 microM). The binding stoichiometry was higher than 1:1 for the main sites of action. In conclusion, bupivacaine exerts its main anaesthetic action on myelinated nerve axons by a direct modification of Na+ channels.
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The present study investigated the possible role of nitric oxide (NO) in the development of the withdrawal contractures of guinea pig isolated ileum after acute activation of mu- and kappa-opioid receptors. After a 4-min in vitro exposure to morphine (mu-opioid receptor preferring, but not selective, agonist), [D-Ala2-N-methyl-Phe4-Gly5-ol-]enkephalin (DAMGO; highly selective mu-opioid receptor agonist), or trans(+/-)-3,4-dichloro-N-methyl-N-2(1-pyrrolidynyl)cyclohexyl-ben zeneacetamide (U50-488H; highly selective kappa-opioid receptor agonist), the guinea-pig isolated ileum exhibited a strong contracture after the addition of naloxone. ⋯ Finally, glyceryl trinitrate on its own (3-300 microM) significantly increased the naloxone-induced contraction after exposure to mu- and kappa-opioid receptor agonist and it was also able to reverse the inhibition of opioid withdrawal caused by L-N(G)-nitro arginine methyl ester. These results provide evidence that NO has a role in the development of opioid withdrawal and that mu- or kappa-opioid receptors are involved.