HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: fj.07-9194comv1 22/5/1317    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Buttigieg, J. Articles by Nurse, C. A. PubMed PubMed Citation Articles by Buttigieg, J. Articles by Nurse, C. A.

Chronic nicotine in utero selectively suppresses hypoxic sensitivity in neonatal rat adrenal chromaffin cells

Josef Buttigieg^*, Stephen Brown^*, Min Zhang^*, Michael Lowe^*, Alison C. Holloway and Colin A. Nurse^*,1

^* Department of Biology, and

Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada

¹Correspondence: Department of Biology, McMaster University, 1280 Main St. West, Hamilton, Ontario, Canada L8S 4K1. E-mail: nursec{at}mcmaster.ca

Nicotine in cigarette smoke has been linked to several deleterious side effects on the offspring of smoking mothers, including impaired development of the sympathoadrenal system, abnormal arousal reflexes, and sudden infant death syndrome. Catecholamine (CA) release from adrenomedullary chromaffin cells (AMCs) in response to asphyxial stressors, e.g., low O₂ (hypoxia) and elevated CO₂ (hypercapnia), is critical for adaptation to extrauterine life and occurs before splanchnic innervation. Here, we investigated the effects of prenatal nicotine bitartrate exposure on the ability of neonatal (P0) rat AMCs to respond appropriately to asphyxial stressors. Control AMCs isolated from pups born to saline-treated dams displayed typical responses to hypoxia and hypercapnia, including inhibition of outward K⁺ current, membrane depolarization, increased cytosolic calcium, and CA secretion. In contrast, P0 AMCs from pups born to nicotine-treated dams showed a marked suppression or loss of hypoxic sensitivity, although hypercapnic sensitivity and the expression of CO₂ markers (i.e., carbonic anhydrase I and II) appeared normal. Moreover, isolated saline-treated P0 AMCs lost their hypoxic sensitivity when grown in culture for 1 wk in the presence of a subsaturating concentration of nicotine base (50 µM), and this effect was abolished by the nicotinic acetylcholine receptor (nAChR) blocker mecamylamine (100 µM). Taken together, these data suggest that the adverse effects of maternal smoking on sympathoadrenal function in the offspring are due in part to a loss or suppression of acute hypoxic sensitivity in adrenal chromaffin cells, triggered by the direct action of nicotine on endogenous nicotinic acetylcholine receptors.—Buttigieg, J., Brown, S., Zhang, M., Lowe, M., Holloway, A. C., Nurse, C. A. Chronic nicotine in utero selectively suppresses hypoxic sensitivity in neonatal rat adrenal chromaffin cells.

Key Words: catecholamine • nAChR • SIDS • fetus • asphyxia