Small-Cell Lung Carcinoma Nicotine Stimulates a Serotonergic Autocrine Loop in Human

Small-cell lung carcinoma cells express different plasma membrane im .n um acetylcholine receptor subtypes. We have now found that inter acting with these receptors (-)-nicotine induces a dose-dependent and stereoselective release of [3H]serotonin which is dependent on external calcium and blocked by the specific ganglionic nicotinic antagonist nice amylamine. With the same potency (-(-nicotine stimulates tumor cell pro liferation, an effect also blocked by mecamylamine. Serotonin itself stimu lates cell proliferation in a dose-dependent manner, an effect blocked by the selective serotonergic receptor antagonists methiotepine and metergoline. These data suggest that nicotine might affect proliferation of smallcell lung carcinoma cells by inducing the release of hormones (such as serotonin) with autocrine capabilities and place both the nicotinic and the serotonergic receptors at key positions in the biological and, possibly, pharmacological approach to this human lung cancer.