Lobeline inhibits nicotine-evoked [(3)H]dopamine overflow from rat striatal slices and nicotine-evoked (86)Rb(+) efflux from thalamic synaptosomes.

The present study evaluated the interaction of lobeline with neuronal nicotinic acetylcholine receptors using two in vitro assays, [(3)H] overflow from [(3)H]dopamine ([(3)H]DA)-preloaded rat striatal slices and (86)Rb(+) efflux from rat thalamic synaptosomes. To assess agonist interactions, the effect of lobeline was determined and compared to S(-)-nicotine. To assess antagonist interactions, the ability of lobeline to inhibit the effect of S(-)-nicotine was determined. Both S(-)-nicotine (0.1-1 microM) and lobeline (>1.0 microM) evoked [(3)H] overflow from superfused [(3)H]DA-preloaded striatal slices. However, lobeline-evoked [(3)H] overflow is mecamylamine-insensitive, indicating that this response is not mediated by nicotinic receptors. Moreover, at concentrations (<1.0 microM) which did not evoke [(3)H] overflow, lobeline inhibited S(-)-nicotine (0.1-10 microM)-evoked [(3)H] overflow, shifting the S(-)-nicotine concentration-response curve to the right. S(-)-Nicotine (30 nM-300 microM) increased (EC(50) value=0.2 microM) (86)Rb(+) efflux from thalamic synaptosomes. In contrast, lobeline (1 nM-10 microM) did not evoke (86)Rb(+) efflux, and the lack of intrinsic activity indicates that lobeline is not an agonist at this nicotinic receptor subtype. Lobeline completely inhibited (IC(50) value=0.7 microM) (86)Rb(+) efflux evoked by 1 microM S(-)-nicotine, a concentration which maximally stimulated (86)Rb(+) efflux. Thus, the results of these in vitro experiments demonstrate that lobeline inhibits the effects of S(-)-nicotine, and suggest that lobeline acts as a nicotinic receptor antagonist.