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This Article Full Text Full Text (PDF) All Versions of this Article: 293/3/L611    most recent 00038.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Wongtrakool, C. Articles by Roman, J. Search for Related Content PubMed PubMed Citation Articles by Wongtrakool, C. Articles by Roman, J.

Nicotine alters lung branching morphogenesis through the ₇ nicotinic acetylcholine receptor

¹Department of Medicine, Division of Pulmonary, Allergy and Critical Care, Emory University School of Medicine, Atlanta; and ²Atlanta Veterans Affairs Medical Center, Decatur, Georgia

Submitted 25 January 2007 ; accepted in final form 31 May 2007

There is abundant epidemiological data linking prenatal environmental tobacco smoke with childhood asthma and wheezing, but the underlying molecular and physiological mechanisms that occur in utero to explain this link remain unelucidated. Several studies suggest that nicotine, which traverses the placenta, is a causative agent. Therefore, we studied the effects of nicotine on lung branching morphogenesis using embryonic murine lung explants. We found that the expression of ₇ nicotinic acetylcholine receptors, which mediate many of the biological effects of nicotine, is highest in pseudoglandular stage lungs compared with lungs at later stages. We then studied the effects of nicotine in the explant model and found that nicotine stimulated lung branching in a dose-dependent fashion. -Bungarotoxin, an antagonist of ₇ nicotinic acetylcholine receptors, blocked the stimulatory effect of nicotine, whereas GTS-21, a specific agonist, stimulated branching, thereby mimicking the effects of nicotine. Explants deficient in ₇ nicotinic acetylcholine receptors did not respond to nicotine. Nicotine also stimulated the growth of the explant. Altogether, these studies suggest that nicotine stimulates lung branching morphogenesis through ₇ nicotinic acetylcholine receptors and may contribute to dysanaptic lung growth, which in turn may predispose the host to airway disease in the postnatal period.

lung growth; nicotinic receptors