Cholinergic-nicotinic control of growth and secretion of cultured pulmonary neuroendocrine cells.
Dispersed newborn hamster lung cells were established in vitro in a defined, low-serum growth medium. Neuroendocrine markers (immunohistochemistry for bombesin/gastrin-releasing peptide and calcitonin) revealed a cellular predominance of pulmonary neuroendocrine (PNE) cells. While the supernatant concentration remained stable, the concentration of PNE cell immunoreactive calcitonin (iCT) gradually declined over 4 weeks. Supplementation of the medium with nicotine for 3 weeks prevented this decline in cellular iCT. Concurrently, the number of cells and [3H]thymidine incorporation were significantly increased. The stimulatory 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 significant increase in iCT in the lungs of newborns; when these lungs were subsequently placed in cell culture without nicotine, despite the higher concentration of iCT, there was a drop in iCT similar to that observed in the control culture. In contrast, in vivo, the lung iCT remained significantly elevated at 1 week post-parturition. Cell culture supernatants were analyzed at week 4 for the evoked release of iCT; cholinergic-nicotinic agonists promptly increased the supernatant iCT, which was blocked by nicotinic but not by muscarinic antagonists. We suggest that this in vitro system provides a useful tool to study directly the PNE cell. The acute and chronic effects of nicotine are most likely related to stimulation of cholinergic-nicotinic receptors on iCT-containing PNE cells.
Department of Physiology, George Washington University School of Medicine, Washington, DC.
E S
ES
Nylen
K L
KL
Becker
R H
RH
Snider
A R
AR
Tabassian
M M
MM
Cassidy
R I
RI
Linnoila
D000818:Animals; D000831:Animals, Newborn; D002116:Calcitonin / Q000032:analysis* / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D008168:Lung / Q000737:chemistry* / Q000166:cytology / Q000187:drug effects / Q000196:embryology; D008647:Mesocricetus; D009490:Neurosecretory Systems / Q000737:chemistry* / Q000166:cytology / Q000187:drug effects / Q000196:embryology; D009538:Nicotine / Q000494:pharmacology*
D009538:Nicotine; D002116:Calcitonin