Effect of inhaled volatile anesthetics on ATP-signal transduction system

吸入挥发性麻醉药对 ATP 信号转导系统的影响

• 批准号: 11671525
• 负责人: MASAKI Eiji
• 金额: $ 2.43万
• 依托单位: Jikei University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671525/
• 关键词: ATP receptor; inhaled anosthetcs; Mechauisws of action; NMDA receptor; interaction; Patch clawp; Gop juuction; Minimuw alreolar concentration; ギャッププジャンクション

This study was undertaken to examine the effects of volatile anesthetics (VA) on ATP signaltransduction system and clarify the involvement of this system in sites and mechanisms of the anesthetics. The experiments were performed both in vivo and in vitro as following.I. In vivo. 1) Effects of the intracerebroventricular (ICV) administration of P2 antagonits on the minimum alveolar concentration (MAC) of VA in rats. 2) The anesthetic interaction between ATP and NMDA receptor agonists in the rats.II. In vitro. 3) Effects of VA on the ATP binding to P2X receptor in the rat brain crude synaptic membrane. 4) Effects of sevoflurane on the ATP-activated inward current in locus coeruleus neurons in pontine slices of rats. 5) Effects of sevoflurane on the recombirtant P2X receptors expressed in HEK 293 cells.Results: I. In vivo. 1) ICV administration of P2 antagonist decreased the MAC of sevoflurane and isoflurane. 2) The effects of coadministration of both ATP and NMDA receptor antagonists was additive in the reduction of sevoflurane MAC.II. In vitro. 3) VA did not affect the ATP binding to P2X receptor. 4) ATP-activated inward current in locus coeruleus neurons was dose-dependentiy reduced by s-evoflurane. 5) The inward currents through P2X2 and P2X4 receptors were suppressed by sevoflurane in raft but not isolated cells.These results suggest that inhibition of ATP signal transduction system is, at least in part, involved in the site and mechanism of VA's mode of action. Furthermore, suppression of signaling through gap junction is also implicated with the site and mechanism of action of VA.

本研究旨在研究挥发性麻醉剂(VA)对ATP信号转导系统的影响，阐明该系统参与麻醉药的作用部位和机制。实验在体内和体外进行如下：1.体内实验。1)侧脑室注射P2受体拮抗剂对大鼠肺泡内VA最低浓度的影响。2)三磷酸腺苷和NMDA受体激动剂在大鼠体内的麻醉相互作用。(3)VA对大鼠脑粗突触膜上ATP与P2X受体结合的影响。4)七氟醚对大鼠脑桥脑片蓝斑神经元ATP激活的内向电流的影响。5)七氟醚对HEK 293细胞表达重组P2X受体的影响。1)侧脑室注射P2拮抗剂可降低七氟醚和异氟醚的MAC。2)三磷酸腺苷和N-甲基-D-天冬氨酸受体拮抗剂联合给药对七氟醚MAC.II的抑制作用是相加的。(3)VA不影响ATP与P2X受体的结合。(4)S-吴茱萸可剂量依赖性地降低蓝斑神经元三磷酸腺苷激活的内向电流。5)七氟醚可抑制RAFT细胞通过P2X2和P2X4受体的内向电流，但不能抑制细胞内向电流。这些结果表明，对ATP信号转导系统的抑制至少部分参与了VA作用方式的部位和机制。此外，通过缝隙连接抑制信号也与VA的作用部位和机制有关。

项目成果

E. Masaki et. al.: "The [^3H]α,β-methylene ATP binding to P2X purinoceptor is not affected by volatile anesthetics"European Journal of Anaesthesiology. in press.

E. Masaki 等人：“[^3H]α,β-亚甲基 ATP 与 P2X 嘌呤受体的结合不受挥发性麻醉剂的影响”《欧洲麻醉学杂志》正在出版。

H.Nishi et al.: "ADP-sensitive purinoceptors induce steroidogensis via adenylyl cyclase activation in bovine adrenocortical fasciculata cells"British Journal of Pharmacology. 137. 177-184 (2002)

H.Nishi等人：“ADP敏感性嘌呤受体通过牛肾上腺皮质束状细胞中的腺苷酸环化酶激活诱导类固醇生成”英国药理学杂志。

E.Masaki et al.: "The [^3H] a, a-methylene ATP binding to P2X purinoceptor is not affected by volatile anesthetics"European Journal of Anaesthesiology. (in press). (2003)

E.Masaki 等人：“与 P2X 嘌呤受体结合的 [^3H]a,a-亚甲基 ATP 不受挥发性麻醉剂的影响”《欧洲麻醉学杂志》。

E.Masaki et al.: "The anesthetic interaction between adenosine triphosphate and N-methyl-D-aspartate receptor antagonists in the rats"Anesthesia and Analgesia. 92. 134-139 (2001)

E.Masaki 等人：“大鼠中三磷酸腺苷和 N-甲基-D-天冬氨酸受体拮抗剂之间的麻醉相互作用”麻醉和镇痛。

E.Masaki et.al.: "Reduction by seroflurane of adenosine 5'-triphosphate-actirated inward curreat of locus coeruleus nearon in pontine slices of rat"Brain Research. 921. 226-232 (2001)

E.Masaki 等人：“通过血清氟烷减少大鼠脑桥切片中蓝斑附近的腺苷 5-三磷酸激活的内向醋栗”大脑研究。