Regulation of cell proliferation by β-adrenergjc receptors in a human lung adenocarcinoma cell line

Abstract
We have recently reported that the tobacco-related nitrosamines N-nitrosodiethylamine (DEN) and 4-(methyl-nitrosamino)-l-(3-pyridyI)-l-butanone (NNK) stimulate cell proliferation in cell tines 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 nkotinic 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 acetykholine receptors and secretion of this cell type is regulated by β-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 β-adrenergk agonist isoproterenol, DEN and NNK, as well as a dose-dependent inhibition of such growth-stimulating effects by the β-adrenergic antagonist propranolol. These findings suggest an important role of β-adrenergic receptors in the regulation of cell proliferation in lung tumors comprised of this cell type.