Inhibition of the neuronal nicotinic receptor-mediated current by kappa opioid receptor agonists in PC12 cells

The authors studied effects of opioid receptor agonists on neuronal nicotinic-receptor-mediated current in PC12 cells using whole-cell current recording. At 1 μM, [D-Ala, N-Me, Phe, Gly-ol]- enkephalin (DAMGO), a selective μ receptor agonist, or 10 μM methionine-enkephalin, a μ and δ receptor agonist, did not inhibit the current elicited by 30 μM nicotine significantly. Dynorphin A (1-17) (0.1-1 μM), an endogenous κ receptor agonist, and U50488 (0.1-10 μM), a non-peptide selective κ receptor agonist, depressed the nicotine-induced current reversibly in a dose- dependent manner. They accelerated the current decay, resulting in greater effects on the nondesensitized current than the peak current. These effects were not affected by nor-binaltrophimine, a selective κ receptor antagonist, or by inclusion of guanosine 5'-O-(2-thiobiphosphate) (GDP[β-S]), a GTP binding protein blocker, into the pipette solution. These results demonstrate that two κ opioid receptor agonists, dynorphin A (1-17) and U50488, inhibit neuronal nicotinic-receptor-mediated current without the involvement of opioid receptors or GTP binding proteins. The acceleration of the current decay suggests a direct action on nicotinic receptors such as open channel block, or augmentation of desensitization. Modulation of neuronal nicotinic receptors by dynorphins may play a role in some areas where dynorphin release sites and neuronal nicotinic receptors are colocalized.