Activation of α1-adrenoceptors facilitates excitatory inputs to medullary airway vagal preganglionic neurons
Activation of α1-adrenoceptors facilitates excitatory inputs to medullary airway vagal preganglionic neurons
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α1-肾上腺素受体的激活促进延髓气道迷走神经节前神经元的兴奋性输入
DOI：
10.1152/japplphysiol.00045.2015
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发表时间：
2015-09-15
影响因子：
3.3
通讯作者：
Wang, Jijiang
中科院分区：
文献类型：
--
作者：
Ge, Dengyun;Yan, Xianxia;Wang, Jijiang
在哺乳动物中，气道平滑肌的神经控制由延髓腹外侧的气道迷走神经节前神经元的子集主导。这些神经元在生理上受肾上腺素能/去甲肾上腺素能投射的调节，并且减弱的α（2）-肾上腺素能对它们的抑制被指示参与哮喘的发病机制和加重。这项研究测试了这些神经元是否受到α（1）-肾上腺素受体的调节，如果是，如何调节。在麻醉的成年大鼠中，将α（1A）-肾上腺素能受体激动剂A61603（1 pmol）单侧微量注射到含有这些神经元的延髓区，引起气道阻力显著增加，腹腔注射阿托品（0.5 mg/kg）可阻止这种增加。在有节奏地发射的新生大鼠延髓切片，A61603（10纳米）引起去极化的吸气激活和吸气抑制气道迷走神经节前神经元，逆行标记，和自发放电率显着增加。在电压钳制下，A61603能显著增强对两种神经元的自发兴奋性输入，并在吸气激活神经元内产生紧张性内向电流，同时沿着吸气内向电流的峰值幅度显著增加。在体外的反应被阻止的α（1A）-肾上腺素受体拮抗剂RS 100329（1 μ M），它单独显着抑制自发兴奋性输入的两种类型的神经元。用河豚毒素（1 μ M）预处理后，A61603（10或100 nM）对两种类型的神经元都没有影响。我们的结论是，在大鼠中，在含有气道迷走神经节前神经元的延髓区的α（1）-肾上腺素受体的激活增加气道迷走神经张力，这种作用主要是通过促进兴奋性输入到节前神经元介导的。
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 alpha(2)-adrenergic inhibition of them is indicated to participate in the pathogenesis and exacerbation of asthma. This study tests whether these neurons are modulated by alpha(1)-adrenoceptors, and if so, how. In anesthetized adult rats, microinjection of the alpha(1A)-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 alpha(1A)-adrenoceptor antagonist RS100329 (1 mu M), which alone significantly inhibited the spontaneous excitatory inputs to both types of the neurons. After pretreatment with tetrodotoxin (1 mu M), A61603 (10 or 100 nM) had no effect on either type of neuron. We conclude that in rats, activation of alpha(1)-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.