Inhibitory effects of psychotomimetic sigma ligands on nicotine-induced K+ flux from differentiated PC12 cells.

In NGF-treated PC12 cells, nicotine-induced K+ release was measured with a K(+)-sensitive microelectrode. The K+ outflow via nicotinic ACh receptor cation channels was inhibited by various psychotomimetic sigma ligands in the sequence of PCP, dextromethorphan >> DTG, MK 801, (+)SKF10047 >> (+)3-PPP. The K+ release was not affected by the neuroleptic sigma ligand haloperidol nor by the calcium antagonist nifedipine. The results suggest that psychotomimetic sigma ligands inhibit nicotine-stimulated K+ flux by interacting with nicotinic, rather than via sigma 2 receptors.