title: Activation of α1-adrenoceptors facilitates excitatory inputs to medullary airway vagal preganglionic neurons.
abstract: In mammals, the neural control of airway smooth muscle is dominated by a subset of airway vagal preganglionic neurons in the ventrolateral medulla. These neurons are physiologically modulated by adrenergic/noradrenergic projections, and weakened α₂-adrenergic inhibition of them is indicated to participate in the pathogenesis and exacerbation of asthma. This study tests whether these neurons are modulated by α₁-adrenoceptors, and if so, how. In anesthetized adult rats, microinjection of the α₁A-adrenoceptor agonist A61603 (1 pmol) unilaterally into the medullary region containing these neurons caused a significant increase in airway resistance, which was prevented by intraperitoneal atropine (0.5 mg/kg). In rhythmically firing medullary slices of newborn rats, A61603 (10 nM) caused depolarization in both the inspiratory-activated and inspiratory-inhibited airway vagal preganglionic neurons that were retrogradely labeled, and a significant increase in the spontaneous firing rate. Under voltage clamp, A61603 significantly enhanced the spontaneous excitatory inputs to both types of neurons and caused a tonic inward current in the inspiratory-activated neurons along with significantly increased peak amplitude of the inspiratory inward currents. The responses in vitro were prevented by α₁A-adrenoceptor antagonist RS100329 (1 μM), which alone significantly inhibited the spontaneous excitatory inputs to both types of the neurons. After pretreatment with tetrodotoxin (1 μM), A61603 (10 or 100 nM) had no effect on either type of neuron. We conclude that in rats, activation of α₁-adrenoceptors in the medullary region containing airway vagal preganglionic neurons increases airway vagal tone, and that this effect is primarily mediated by facilitation of the excitatory inputs to the preganglionic neurons.
authors.affiliation: Department of Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai, China;
authors.forename: Dengyun
authors.initials: D
authors.lastname: Ge
authors.affiliation: Department of Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai, China;
authors.forename: Xianxia
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai, China;
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai, China;
authors.forename: Xingxin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China; and.
authors.forename: Ruijuan
authors.initials: R
authors.lastname: Guan
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China; and.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Gerontology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Dongying
authors.initials: D
authors.lastname: Qiu
authors.affiliation: Department of Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai, China; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China; and wangjj@shmu.edu.cn.
authors.forename: Jijiang
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology; D012137:Respiratory System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D014630:Vagus Nerve / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology
chemical_list: D018340:Receptors, Adrenergic, alpha-1; D013779:Tetrodotoxin
keywords: adrenoceptor; airway; patch clamp; preganglionic; synapse