The Role of Alpha-2 Adrenergic Receptors in the Action of Anesthetics and Analgesics

Alpha-2 肾上腺素受体在麻醉和镇痛药作用中的作用

• 批准号: 01480378
• 负责人: SAKABE Takefumi
• 金额: $ 2.37万
• 依托单位: Yamaguchi University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1990
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-01480378/
• 关键词: anesthetics; analgesics; nitrous oxide; halothane; pentobarbital; morphine; noradrenaline; alpha-2 receptor; in vitro autoradiography

The present study was designed to examine the role of central noradrenergic system, especially alpha-2 adrenergic receptors in the action of various anesthetics and analgesics;nitrous oxide 75%, halothane 1.3%, pentobarbital 80mg/kg (ip), and morphine 5mg/kg (iv). Male Wistar rats were used. Analgesic effects of drugs were evaluated by the tail-flick test and response latencies were expressed as the percentage of the maximal possible effect (%MPE). Effects of combined use of alpha-2 adrenergic agonist, clonidine (150mug/kg), were also examined. Noradrenaline concentrations and alpha-2 receptor bindings in the brain and spinal cord were measured, using high performance liquid chromatography and "in vitro" receptor autroadiography (ligand ; [_3H]-clonidine). Modulation of analgesic effect of nitrous oxide by a stress (capture in the steel nets), lesion to the locus coeruleus, and anloxone were also examined.Nitrous oxide and morphine produced analgesia (%MPE 60% and 100%, ), but neither halothane nor pentobarbital did. Clonidine produced analgesia (%MPE 20-40%) in the awake rat. When it was comined with nitrous oxide, analgesic effect of nitrous oxide was sustained. With halothane and pentobarbital, it produced analgesia (%MPE 60-75% and 80-100%). In nitrous oxide-induced analgesia, there was a decrease in noradrenaline concentration and an increase in the binding of [_3H]-clonidine in the locus coeruleus and dorsal horn of the spinal cord. Locus coeruleuslesion markedly attenuated nitrous oxide-induced analgesia, while neither naloxone nor stress attenuated it.It is concluded that clonidine produces (or potentiates) analgesic effects of various drugs and that the analgesic effect of nitrous oxide is attributed to the effect on the central noradrenergic system, possibly by an activation of the descending inhibitory system and/or inhibition of the primary sensory afferent neuron via alpha-2 adrenergic receptors.

本实验旨在研究中枢去甲肾上腺素能系统，特别是α 2肾上腺素能受体在各种麻醉药和镇痛药（75%笑气，1.3%氟烷，80 mg/kg戊巴比妥，5 mg/kg吗啡）作用中的作用。使用雄性Wistar大鼠。通过甩尾试验评价药物的镇痛作用，并将反应延迟表示为最大可能作用的百分比（%MPE）。还检查了联合使用α-2肾上腺素能激动剂可乐定（150 μ g/kg）的作用。使用高效液相色谱法和“体外”受体放射自显影（配体; [_3H]-可乐定）测定脑和脊髓中去甲肾上腺素浓度和α-2受体结合。笑气和吗啡产生镇痛作用（%MPE 60%和100%），氟烷和戊巴比妥均不产生镇痛作用。可乐定在清醒大鼠中产生镇痛作用（%MPE 20-40%）。与笑气合用时，笑气的镇痛作用持续。与氟烷和戊巴比妥，它产生镇痛（%MPE 60-75%和80-100%）。在氧化亚氮诱导的镇痛中，蓝斑和脊髓背角的去甲肾上腺素浓度降低，[_3H]-可乐定结合增加。损毁蓝斑可明显减弱一氧化氮的镇痛作用，而纳洛酮和应激均不减弱其镇痛作用。（或增强）各种药物的镇痛作用，并且一氧化二氮的镇痛作用归因于对中枢去甲肾上腺素能系统的作用，可能通过激活下行抑制系统和/或通过α-2肾上腺素能受体抑制初级感觉传入神经元。

项目成果

Ishikawa T. et al.: "Interaction of clonidine with anesthetics through a modulation of neurotransmission." J Neurochemistry.

Ishikawa T. 等人：“可乐定通过调节神经传递与麻醉剂相互作用。”

Sakabe T. et al.: "Does clonidine potentiate nitrous oxide induced analgesia in rats?" Brain Research.

Sakabe T. 等人：“可乐定是否能增强一氧化二氮诱导的大鼠镇痛作用？”

Sakabe T. et al.: "Modification of anesthetic actions by alpha_2 receptor agonist, clonidine, in the rat." Anesthesiology.

Sakabe T. 等人：“α_2 受体激动剂可乐定对大鼠麻醉作用的改变。”

Sakabe T.et al.: "Modification of anesthetic actions by α_2 receptor agonist,clonidine,in the rat." Anesthesiology.

Sakabe T. 等人：“α_2 受体激动剂可乐定对大鼠麻醉作用的改变。”

Sakabe T.et al.: "Modification of anestnetic actions by α_2 receptor agonist, clonidine,in the rat." Anesthesiology.

Sakabe T. 等人：“α_2 受体激动剂可乐定对大鼠麻醉作用的改变。”