Wilson Christopher G, Akhter Shamima, Mayer Catherine A, Kc Prabha, Balan Kannan V, Ernsberger Paul, Haxhiu Musa A
Department of Pediatrics, Case Western Reserve University, School of Medicine, Cleveland, OH 44106-6010, USA.
J Appl Physiol (1985). 2007 Dec;103(6):2095-104. doi: 10.1152/japplphysiol.01182.2006. Epub 2007 Sep 13.
Brain stem noradrenergic cell groups mediating autonomic responses to stress project to airway-related vagal preganglionic neurons (AVPNs). In ferrets, their activation produces withdrawal of cholinergic outflow to the airways via release of norepinephrine and activation of alpha(2A)-adrenergic receptors (alpha(2A)-AR) expressed by AVPNs. In these studies, we examined the effects of allergen exposure of the airway (AE) with ovalbumin on noradrenergic transmission regulating the activity of AVPNs and, consequently, airway smooth muscle tone. Experiments were performed in vehicle control (Con) and AE ferrets. Microperfusion of an alpha(2A)-AR agonist (guanabenz) in close proximity to AVPNs elicited more pronounced effects in Con than AE ferrets, including a decrease in unit activity and reflexly evoked responses of putative AVPN neurons with a corresponding decrease in cholinergic outflow to the airways. Although no differences were found in the extent of noradrenergic innervation of the AVPNs, RT-PCR and Western blot studies demonstrated that AE and repeated exposure to antigen significantly reduced expression of alpha(2A)-ARs at message and protein levels. These findings indicate that, in an animal model of allergic asthma, sensitization and repeated challenges with a specific allergen diminish central inhibitory noradrenergic modulation of AVPNs, possibly via downregulation of alpha(2A)-AR expression by these neurons.
介导对应激的自主反应的脑干去甲肾上腺素能细胞群投射至与气道相关的迷走神经节前神经元（AVPNs）。在雪貂中，它们的激活通过去甲肾上腺素的释放以及AVPNs表达的α（2A）-肾上腺素能受体（α（2A）-AR）的激活，导致气道胆碱能流出减少。在这些研究中，我们研究了用卵清蛋白对气道进行变应原暴露（AE）对调节AVPNs活性进而调节气道平滑肌张力的去甲肾上腺素能传递的影响。实验在载体对照（Con）雪貂和AE雪貂中进行。在靠近AVPNs处微量灌注α（2A）-AR激动剂（胍那苄）在Con雪貂中比在AE雪貂中引起更明显的效应，包括单位活动减少以及假定的AVPN神经元的反射诱发反应减少，同时气道胆碱能流出相应减少。尽管在AVPNs的去甲肾上腺素能神经支配程度上未发现差异，但逆转录-聚合酶链反应（RT-PCR）和蛋白质印迹研究表明，AE和重复暴露于抗原显著降低了α（2A）-ARs在信使和蛋白质水平的表达。这些发现表明，在过敏性哮喘动物模型中，对特定变应原的致敏和重复激发可能通过这些神经元α（2A）-AR表达的下调，减弱了AVPNs的中枢抑制性去甲肾上腺素能调制。
