Agonist of 5-HT_1A/7 receptors but not that of 5-HT₂ receptors disinhibits tracheobronchial-projecting airway vagal preganglionic neurons of rats

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• 作者：Y. Chen^a ; ¹ ; L. Wang^a ; ¹ ; X. Zhou^a ; D. Ge^a ; W. Yuan^b ; J. Wang^a ; ^{wangjj@shmu.edu.cn}
• 关键词：5-HT ; synapse ; airway ; vagal ; preganglionic ; neuron
• 刊名：Neuroscience
• 出版年：2012
• 期刊代码：50_03064522
• 类别：neu
• 出版时间：5 April, 2012
• 卷：207
• 期：Complete
• 页码：78-87
• 文件大小：2782 K

摘要

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-HT_1A/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 cl and the effects of 5-HT_1A/7 receptor agonist (卤)-8-Hydroxy-2-(dipropylamino) tetralin hydrobromide (8-OH-DPAT) (1 渭mol L^鈭?) and 5-HT₂ receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (10 渭mol L^鈭?) 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-HT_1A/7 receptor antagonist N-[2-[4-(2-Methoxyphenyl)-1-piperazinyl] ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate salt (WAY-100635) (1 渭mol L^鈭?). 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-HT_1A/7 receptor agonist causes 鈥渄isinhibition鈥?of T-AVPNs, which might, in part, account for the reflex increase of airway resistance.