Huang Z G, Griffioen K J S, Wang X, Dergacheva O, Kamendi H, Gorini C, Mendelowitz D
Department of Pharmacology and Physiology, The George Washington University, Washington, DC 20037, USA.
J Neurophysiol. 2007 Oct;98(4):2429-38. doi: 10.1152/jn.00448.2007. Epub 2007 Aug 15.
Prenatal nicotine exposure alters the cardiorespiratory network responses to hypoxia/hypercapnia; however the mechanism(s) responsible for these cardiorespiratory network responses and their alteration by prenatal nicotine exposure are unknown. We used an in vitro medullary slice that allows simultaneous examination of rhythmic respiratory-related activity and excitatory synaptic neurotransmission to cardioinhibitory vagal neurons (CVNs). Respiratory related increases in glutamatergic neurotransmission only occurred on recovery from hypoxia/hypercapnia in unexposed animals. These responses were not altered by nicotinic antagonists but were mediated in part by activation of P2 purinergic receptors. Prenatal nicotine exposure transformed central cardiorespiratory responses to hypoxia/hypercapnia; CVNs received a respiratory related glutamatergic neurotransmission during periods of hypoxia and hypercapnia, whereas increases in glutamatergic neurotransmission during recovery were absent. The excitatory neurotransmission to CVNs during hypoxia/hypercapnia in prenatal nicotine-exposed animals were wholly dependent on nicotinic receptor activation. In the presence of nicotinic antagonists, the responses in prenatal nicotine animals reverted to the pattern of responses in unexposed animals in which an increase in glutamatergic neurotransmission occurred not during but only on recovery from hypoxia/hypercapnia, and this recruited excitatory pathway was blocked by P2 receptor antagonists. These data identify a new functional role for purinergic receptors in the cardiorespiratory responses to hypoxia/hypercapnia and their role in occluding nicotinic receptor activation with prenatal nicotine exposure.
产前尼古丁暴露会改变心肺网络对低氧/高碳酸血症的反应；然而，导致这些心肺网络反应及其因产前尼古丁暴露而改变的机制尚不清楚。我们使用了一种体外延髓切片，它能够同时检测与呼吸相关的节律性活动以及对心抑制性迷走神经元（CVNs）的兴奋性突触神经传递。在未暴露的动物中，谷氨酸能神经传递的呼吸相关增加仅在从低氧/高碳酸血症恢复时出现。这些反应不受烟碱拮抗剂的影响，但部分是由P2嘌呤能受体的激活介导的。产前尼古丁暴露改变了中枢对低氧/高碳酸血症的心肺反应；在低氧和高碳酸血症期间，CVNs会接收到与呼吸相关的谷氨酸能神经传递，而恢复期间谷氨酸能神经传递的增加则不存在。产前尼古丁暴露动物在低氧/高碳酸血症期间对CVNs的兴奋性神经传递完全依赖于烟碱受体的激活。在存在烟碱拮抗剂的情况下，产前尼古丁暴露动物的反应恢复到未暴露动物的反应模式，即谷氨酸能神经传递的增加不是在低氧/高碳酸血症期间发生，而是仅在从低氧/高碳酸血症恢复时出现，并且这种募集的兴奋性途径被P2受体拮抗剂阻断。这些数据确定了嘌呤能受体在心肺对低氧/高碳酸血症反应中的新功能作用，以及它们在产前尼古丁暴露时阻断烟碱受体激活中的作用。
