Buttigieg Josef, Brown Stephen, Zhang Min, Lowe Michael, Holloway Alison C, Nurse Colin A
Department of Biology, McMaster University, 1280 Main St. West, Hamilton, Ontario, Canada L8S 4K1.
FASEB J. 2008 May;22(5):1317-26. doi: 10.1096/fj.07-9194com. Epub 2007 Dec 10.
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 O(2) (hypoxia) and elevated CO(2) (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 CO(2) 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 approximately 1 wk in the presence of a subsaturating concentration of nicotine base (50 microM), and this effect was abolished by the nicotinic acetylcholine receptor (nAChR) blocker mecamylamine (100 microM). 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.
香烟烟雾中的尼古丁与吸烟母亲的后代出现的几种有害副作用有关，包括交感肾上腺系统发育受损、异常觉醒反射和婴儿猝死综合征。肾上腺髓质嗜铬细胞（AMCs）在应对窒息应激源（如低氧（缺氧）和高二氧化碳（高碳酸血症））时释放儿茶酚胺（CA），这对于适应宫外生活至关重要，且发生在内脏神经支配之前。在此，我们研究了产前暴露于酒石酸尼古丁对新生（P0）大鼠AMCs对窒息应激源做出适当反应能力的影响。从盐水处理母鼠所生幼崽中分离出的对照AMCs对缺氧和高碳酸血症表现出典型反应，包括外向钾电流抑制、膜去极化、胞质钙增加和CA分泌。相比之下，尼古丁处理母鼠所生P0 AMCs对缺氧敏感性明显受到抑制或丧失，尽管对高碳酸血症的敏感性和二氧化碳标志物（即碳酸酐酶I和II）的表达看起来正常。此外，在亚饱和浓度尼古丁碱（50 microM）存在下，分离出的盐水处理P0 AMCs在培养约1周后失去了缺氧敏感性，且这种作用被烟碱型乙酰胆碱受体（nAChR）阻滞剂美加明（100 microM）消除。综上所述，这些数据表明，母亲吸烟对后代交感肾上腺功能的不利影响部分归因于尼古丁对内源性烟碱型乙酰胆碱受体的直接作用引发的肾上腺嗜铬细胞急性缺氧敏感性的丧失或抑制。
