Regulation of cell proliferation by beta-adrenergic receptors in a human lung adenocarcinoma cell line.

We have recently reported that the tobacco-related nitrosamines N-nitrosodiethylamine (DEN) and 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) stimulate cell proliferation in cell lines derived from human neuroendocrine carcinoma and adenocarcinoma (comprised of Clara cells) of the lung. In the neuroendocrine cell line, this effect was inhibited by antagonists of nicotinic cholinergic receptors which regulate the secretion of peptide hormones and cell proliferation of pulmonary neuroendocrine cells. No such inhibition was observed in the adenocarcinoma line. Clara cells reportedly do not have acetylcholine receptors and secretion of this cell type is regulated by beta-adrenergic receptors instead. In this experiment, we test the hypothesis that the latter types of receptors are involved in the regulation of cell growth of normal and nitrosamine-stimulated adenocarcinoma cells with features of Clara cells. Our data demonstrate a pronounced stimulation of cell growth by the beta-adrenergic agonist isoproterenol, DEN and NNK, as well as a dose-dependent inhibition of such growth-stimulating effects by the beta-adrenergic antagonist propranolol. These findings suggest an important role of beta-adrenergic receptors in the regulation of cell proliferation in lung tumors comprised of this cell type.