Possible expression of a sigma 1 site in rat pheochromocytoma (PC12) cells

To examine the functional interaction between the sigma binding sites and nicotinic acetylcholine receptors, we investigated the effects of various sigma receptor ligands on nicotine-evoked Ca2+ uptake in differentiated PC12 cells. The IC50 values of sigma receptor ligands tested in this uptake study did not correlate with their Ki values in the [3H]1, 3-di(2-tolyl) guanidine ([3H]DTG) binding to guinea pig brain reported by Rothman et al. (1991). To clarify further the binding characteristics of the sigma binding sites on PC12 cells, we examined the effects of sigma receptor ligands on [3H]N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine HCl ([3H]NE-100) binding to PC12 membranes. The Ki values of the various drugs tested for [3H]NE-100 binding site closely correlated with their Ki values for the DTG site-1 reported by Rothman et al. (1991). This study showed that PC12 cells express sigma 1-like sites and the inhibitory effect of sigma receptor ligands on the nicotine-evoked Ca2+ uptake was not directly coupled with either the sigma 1 or sigma 2 sites.