CHOLINERGIC-NICOTINIC CONTROL OF GROWTH AND SECRETION OF CULTURED PULMONARY NEUROENDOCRINE CELLS

Dispersed newborn hamster lung cells were established in vitro in a de fined, low-serum growth medium. Neuroendocrine markers (immunohistoche mistry for bombesin/gastrin-releasing peptide and calcitonin) revealed a cellular predominance of pulmonary neuroendocrine (PNE) cells. Whil e the supernatant concentration remained stable, the concentration of PNE cell immunoreactive calcitonin (iCT) gradually declined over 4 wee ks. Supplementation of the medium with nicotine for 3 weeks prevented this decline in cellular iCT. Concurrently, the number of cells and [H -3]thymidine incorporation were significantly increased. The stimulato ry effect of chronic nicotine was reversed by the coadministration of the nicotinic antagonist hexamethonium. In another set of experiments, prior multiple transplacental nicotine pretreatments resulted in a si gnificant increase in iCT in the lungs of newborns; when these lungs w ere subsequently placed in cell culture without nicotine, despite the higher concentration of iCT, there was a drop in iCT similar to that o bserved in the control culture. In contrast, in vivo, the lung iCT rem ained significantly elevated at 1 week postparturition. Cell culture s upernatants were analyzed at week 4 for the evoked release of iCT; cho linergic-nicotinic agonists promptly increased the supernatant iCT, wh ich was blocked by nicotinic but not by muscarinic antagonists. We sug gest that this in vitro system provides a useful tool to study directl y the PNE cell. The acute and chronic effects of nicotine are most lik ely related to stimulation of cholinergic-nicotinic receptors on iCT-c ontaining PNE cells.