AGONIST OF 5-HT1A/7 RECEPTORS BUT NOT THAT OF 5-HT2 RECEPTORS DISINHIBITS TRACHEOBRONCHIAL-PROJECTING AIRWAY VAGAL PREGANGLIONIC NEURONS OF RATS
AGONIST OF 5-HT1A/7 RECEPTORS BUT NOT THAT OF 5-HT2 RECEPTORS DISINHIBITS TRACHEOBRONCHIAL-PROJECTING AIRWAY VAGAL PREGANGLIONIC NEURONS OF RATS
复制标题
5-ht1a/7 受体激动剂而非 5-ht2 受体激动剂抑制大鼠气管支气管投射气道迷走神经节前神经元
DOI：
10.1016/j.neuroscience.2012.01.047
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发表时间：
2012-04-05
期刊：
影响因子：
3.3
通讯作者：
Wang, J.
中科院分区：
文献类型：
--
作者：
Chen, Y.;Wang, L.;Wang, J.
迷走神经在生理上为气道平滑肌提供主要的胆碱能张力，在某些病理条件下，迷走神经在气道高反应性的发生中起关键作用。节后气道胆碱能张力在很大程度上依赖于延髓气道迷走神经节前神经元(AVPN)的持续活动，其中投射气管、支气管的神经元主要位于疑核(Ena)的外部结构中。AVPN受5-羟色胺(5-HT1/7)和5-HT2受体的调节。但突触水平的机制尚不清楚。在本研究中，从气管壁逆行标记了气管-支气管壁投射的AVPN(T-AVPN)，用全细胞电压膜片钳记录了在Ena内荧光标记的T-AVPN，并观察了5-HT1a/7受体激动剂(+/-)-8-羟基-2-(二丙氨基)氢溴酸四氢呋喃(8-OH-DPAT)(1mU/L)和5-HT2受体激动剂1-(2，5-二甲氧基-4-碘苯基)-2-氨基丙烷(DOI)(10mU/L)对突触传入的影响。8-OH-DPAT在频率和幅度上均明显抑制T-AVPN的GABA能和甘氨酸能自发抑制性突触后电流(SIPSCs)，但对GABA能和甘氨酸能微小抑制性突触后电流(MIPSCs)无明显影响。受体拮抗剂N-[2-[4-(2-甲氧基苯基)-1-哌嗪基]乙基]-N-2-吡啶基环己甲酰胺马来酸盐(WAY-100635)(1mU·moL L-1)可阻断8-OH-DPAT对GABA能和甘氨酸能SIPSCs的抑制作用。8-OH-DPAT对谷氨酸能自发兴奋性突触后电流(SEPSCs)无影响，对T-AVPN的基础电流和输入电阻也无影响。DOI对T-AVPN的任何类型的突触输入均无影响。这些结果表明，5-HT1A/7受体激动剂引起T-AVPN的“去抑制”，这可能是导致呼吸道阻力反射性增加的部分原因。(C)2012年IBRO。爱思唯尔有限公司出版。保留所有权利。
The vagus nerves supply the major cholinergic tone to airway smooth muscles physiologically and play critical roles in the genesis of airway hyperreactivity under some pathological conditions. Postganglionic airway cholinergic tone relies largely on the ongoing activity of medullary airway vagal preganglionic neurons (AVPNs), of which the tracheobronchial-projecting ones are primarily located in the external formation of the nucleus ambiguus (eNA). AVPNs are regulated by 5-HT, and 5-HT1A/7 and 5-HT2 receptors have been indicated to be involved. But the mechanisms at synaptic level are unknown. In the present study, tracheobronchial-projecting AVPNs (T-AVPNs) were retrogradely labeled from the trachea wall; fluorescently labeled T-AVPNs in the eNA were recorded with whole-cell voltage patch clamp; and the effects of 5-HT1A/7 receptor agonist (+/-)-8-Hydroxy-2-(dipropylamino) tetralin hydrobromide (8-OH-DPAT) (1 mu mol L-1) and 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (10 mu mol L-1) on the synaptic inputs were examined. 8-OH-DPAT significantly inhibited the GABAergic and glycinergic spontaneous inhibitory postsynaptic currents (sIPSCs) of T-AVPNs in both the frequency and amplitude but had no effect on the GABAergic and glycinergic miniature inhibitory postsynaptic currents (mIPSCs). The 8-OH-DPAT inhibition of the GABAergic and glycinergic sIPSCs was prevented by 5-HT1A/7, receptor antagonist N-[2-[4-(2-Methoxyphenyl)-1-piperazinyl] ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate salt (WAY-100635) (1 mu mol L-1). 8-OH-DPAT had no effect on the glutamatergic spontaneous excitatory postsynaptic currents (sEPSCs) and caused no alterations in the baseline current and input resistance of T-AVPNs. DOI had no effect on any types of the synaptic inputs of T-AVPNs. These results suggest that 5-HT1A/7 receptor agonist causes "disinhibition" of T-AVPNs, which might, in part, account for the reflex increase of airway resistance. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.