Interaction of tobacco-specific toxicants with nicotinic cholinergic regulation of fetal pulmonary neuroendocrine cells: Implications for pediatric lung disease
Interaction of tobacco-specific toxicants with nicotinic cholinergic regulation of fetal pulmonary neuroendocrine cells: Implications for pediatric lung disease
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DOI：
10.1080/019021400269916
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发表时间：
2000-03-01
影响因子：
1.7
通讯作者：
Schuller, HM
中科院分区：
文献类型：
--
作者：
Plummer, HK;Sheppard, BJ;Schuller, HM
Pulmonary neuroendocrine cells (PNEC) produce neuropeptides and biogenic amines which regulate pulmonary vasoconstriction and bronchoconstriction. Increased numbers of PNEC along with elevated levels of their products have been consistently observed in a variety of pediatric pulmonary diseases, some of which are etiologically linked with prenatal exposure to cigarette smoke, and all of which are exacerbated by passive smoking. The objective of our studies was to characterize the autonomic regulation of these cells and to explore a potential direct interaction of tobacco-specific toxicants with these regulatory pathways. Using reverse transcription polymerase chain reaction (RT-PCR), radioreceptor assays, flow cytometry, enzyme-linked immunosorbent assay (ELISA), and cell proliferation assays, we found that the release of serotonin from fetal PNEC is regulated by a neuronal alpha(7)-nicotinic acetylcholine receptor (alpha(7)-nA ChR) via a Ca2+-dependent mechanism. The tobacco-specific toxicants nicotine and 4-(methylnitrosamino)-1-(-3-pyridine)-1-butanone (NNK) bound with high affinity to this receptor, resulting in influx of Ca2+, release of serotonin, and stimulation of DNA synthesis. Chronic stimulation of the alpha(7)-nA ChR in the fetal lungs by prenatal exposure to cigarette smoke may contribute to the development of smoking-related pediatric pulmonary disease, whereas postnatal chronic exposure to environmental smoke may exacerbate these Pediatric diseases via direct interaction with this receptor.
