Neurochemical regulation of cough response to capsaicin in guinea-pigs.

Neurochemical regulation of cough response to capsaicin in guinea-pigs.
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DOI:
10.1046/j.1474-8673.2002.00242.x
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发表时间:
2002-02-01
期刊:
Autonomic & Autacoid Pharmacology
影响因子:
--
通讯作者:
Sasaki, H.
Sasaki, H.
中科院分区:
其他
文献类型:
--
作者:
Li, J. Q.;Jia, Y. X.;Sasaki, H.

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虽然已经做出了巨大的努力来确定咳嗽的作用部位,但神经递质系统在咳嗽反射中的重要性受到的关注有限。我们研究了四种主要神经递质(乙酰胆碱、组胺、5-羟色胺和多巴胺)在咳嗽反射调制中的作用。本文观察了阿托品(M胆碱能阻断剂)、马来酸吡拉明(PM,组胺H_1阻断剂)、西咪替丁(组胺H_2阻断剂)、8-羟基-2-(二正丙基氨基)-四氢萘(8-OH-DPAT,特异性5-HT_(1A)受体激动剂)和SCH-23390(选择性多巴胺D_1受体拮抗剂)对清醒豚鼠吸入辣椒素引起的咳嗽反应。所有药物均以剂量依赖性方式显著减少辣椒素诱导的咳嗽次数。为了比较这些药物对咳嗽反应的敏感性,我们计算了当动物暴露于3 × 10-4 M辣椒素时咳嗽50%抑制的有效剂量(ED 50)。阿托品的ED 50值为0.03 μ M kg-1,8-OH-DPAT为0.2 μ M kg-1,SCH-23390为6.2 μ M kg-1,PM为8.5 μ M kg-1,西咪替丁为13.9 μ M kg-1。提示这四种神经递质均参与咳嗽反射的调节。中枢神经系统疾病中这些神经递质的多种变化可能协同影响咳嗽反射。
Although monumental efforts have been made to define the action sites of cough, the importance of neurotransmitter systems in the cough reflex has received limited attention. We studied the roles for four major neurotransmitters (acetylcholine, histamine, serotonin (5-hydroxytryptamine, 5-HT) and dopamine) in the modulation of the cough reflex. Atropine (muscarinic cholinergic blocking agent), pyrilamine maleate (PM, histamine H1 blocker), cimetidine (histamine H2 blocker), 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT, specific 5-HT1A receptor agonist) and SCH-23390 (selective dopamine D1 receptor antagonist) were examined on the cough response to inhaled capsaicin in conscious guinea-pigs. All the drugs significantly decreased the number of capsaicin-induced coughs in a dose-dependent manner. To compare the sensitivity of these drugs on cough response, we calculated the effective doses for 50% inhibition of cough (ED50) when the animals were exposed to 3 X 10-4 M capsaicin. The ED50 values were 0.03 muM kg-1 for atropine, 0.2 muM kg-1 for 8-OH-DPAT, 6.2 muM kg-1 for SCH-23390, 8.5 muM kg-1 for PM and 13.9 muM kg-1 for cimetidine. These findings indicated that all these four neurotransmitters may be involved in the regulation of the cough reflex. Multiple changes of these neurotransmitters in disorders of the central nervous system might synergically affect the cough reflex.