A μ-opioid receptor agonist DAMGO induces rapid breathing in the arterially perfused in situ preparation of rat
A μ-opioid receptor agonist DAMGO induces rapid breathing in the arterially perfused in situ preparation of rat
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DOI：
10.1016/j.resp.2011.04.002
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发表时间：
2011-07-31
影响因子：
2.3
通讯作者：
Oku, Yoshitaka
中科院分区：
文献类型：
--
作者：
Koganezawa, Tadachika;Okada, Yasumasa;Oku, Yoshitaka
对阿片类药物的呼吸反应是复杂的，尚未完全了解。我们研究了选择性Mu阿片受体激动剂[D-Ala(2)，N-Me-Phe(4)，Gly(5)-ol]-Enkephalin(DAMGO)对动脉灌流大鼠在体肺输出量的浓度依赖效应，以维持桥脑-延髓呼吸网络的完整性。向灌流液中累加DAMGO(300~3400 nm)。DAMGO可延长吸气时间，减少中枢迷走神经吸气后活动。在300-500 nm处，DAMGO引起呼吸急促，呼气时间缩短。呼吸模式的改变发生在一次呼吸中。双侧迷走神经切断对呼吸模式的改变没有影响，表明它是中枢起源的。额外的DAMGO直到1800 NM不影响快速呼吸模式，进一步升高的浓度(直到3400 NM)导致不一致的结果。由于快速呼吸模式与迷走神经吸气后活动的消失有关，我们得出结论，DAMGO将呼吸输出重新配置为吸气相占主导地位的快速交替的吸气-呼气模式。(C)2011爱思唯尔B.V.保留所有权利。
Ventilatory responses to opioids are complex and not yet fully understood. We evaluated concentration-dependent effects of a selective mu-opioid receptor agonist [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO) on respiratory output in the arterially perfused in situ rat preparation, which preserves the integrity of the ponto-medullary respiratory network. DAMGO (300-3400 nM) was added accumulatively to the perfusate. DAMGO increased inspiratory time and diminished central vagal post-inspiratory activity. At 300-500 nM DAMGO caused rapid breathing with shortening of expiratory time. The change of breathing pattern occurred within a single breath. Bilateral vagotomy did not affect the change in respiratory pattern, suggesting that it was of central origin. Additional DAMGO up to 1800 nM did not affect the rapid breathing pattern, and further elevated concentrations (up to 3400 nM) caused inconsistent results. Since the rapid breathing pattern was associated with the obliteration of vagal post-inspiratory activity, we conclude that DAMGO reconfigures the respiratory output to an inspiratory phase-dominant, rapidly alternating inspiration-expiration pattern. (C) 2011 Elsevier B.V. All rights reserved.