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Anesthesia and Pain Signal transmission and Control Mechanisms of Ion transporters

麻醉与疼痛离子转运蛋白的信号传递与控制机制

基本信息

批准号：
14207059
负责人：
DOHI Shuji
金额：
$ 20.55万
依托单位：
Gifu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14207059/
关键词：
signaling molecules ion transportor Na^+-K^+ATPase inhibitor Na+-K^+-2Cl^-Na+ channels local anesthetics lidocaine NMDA antagonists 抗不整脈薬 Na^+チャネル NMDAアンタゴニスト DRGニューロン use-dependent bloc 脊髄鎮痛機構 Na^+-H^+の阻害薬 Na^+-K^+-2Cl^- co

项目摘要

Although the action of ion-transporters is vital in living cell and organisms, there have been only few studies in which roles of ion-transporters have been investigated on the aspect of anesthesia and pain transmission. Since we have examined how local anesthetics could affect Na^+-K^+ATPase (Na pump) activity using in vivo experiments of rats. We found that since their inhibitors administered into spinal subarachinoid caused significant antinociceptive action, Na^+-K^+ATPase (Na pump) and Na^+-H^+ exchanger would have significant role in local anesthetic action at the spinal cord level, but not with Na^+-K^+-2CL cotranspoter. Oubabain and amiloride seem not to affect signaling molecules such as mitogen-activated protein kinase (MAPK) family members, extracellular signal-regulated kinases (ERKs), PKC, and PLC. Local anesthetic tetracaine induces apoptosis of PC12 cells via phosphorylation of MAPK family. ERK activation protects cells from death, but JNK plays the opposite role. Toxic Ca^<2+> influx caused by tetracaine seems to be responsible for apoptotic cell death, but blocking of Na^+ channels and L-type Ca^<2+> channels is unlikely involved in such tetracaine's action on signaling molecules for apoptosis. Using neuronal acitivity of rat's dorsal root ganglion we also found that NMDA receptor antagonists such as ketamine and ifenprodil, as well as Class 1c antiarrhythmics such as flecainide and pilsicainide could also affect TTX resistant Na+ channel activity. Using cardiac myocytes, intravenous anesthetics, midazolam suppresses thrombin-induced heat shock protein 27 phosphorylation through inhibition of p38 mitogen-activated protein kinaseOur studies indicate that local anesthetics as well as intravenous anesthetics used clinically could affect ion channel and ion-transporters via modulation of intracellular signaling molecules. The results suggested that such action would seem to play some roles in anesthetic action and pain transmission.

虽然离子转运蛋白在活细胞和生物体中的作用是至关重要的，但只有少数研究在麻醉和疼痛传递方面研究了离子转运蛋白的作用。我们已经通过大鼠体内实验研究了局麻药对Na^+-K^+ ATP酶（Na泵）活性的影响。我们发现，由于在脊髓蛛网膜下腔注射Na^+-K^+ ATP酶（Na泵）和Na^+-H^+交换酶抑制剂可产生显著的抗伤害性作用，因此它们在脊髓水平的局麻作用中可能发挥重要作用，但Na^+-K^+-2CL共转运酶则不起作用。乌巴因和阿米洛利似乎不影响信号分子，如丝裂原活化蛋白激酶（MAPK）家族成员，细胞外信号调节激酶（ERK），PKC和PLC。局麻药丁卡因通过磷酸化MAPK家族诱导PC 12细胞凋亡ERK的激活保护细胞免于死亡，而JNK则起相反的作用。丁卡因引起的毒性Ca^<2+>内流似乎是导致细胞凋亡的原因，但Na^+通道和L型Ca^<2+>通道的阻断不太可能参与丁卡因对细胞凋亡信号分子的作用。利用大鼠背根神经节神经元的活动，我们还发现NMDA受体拮抗剂如氯胺酮和艾芬地尔，以及1c类抗甲状腺药物如氟卡尼和匹西卡尼也能影响TTX抗性Na+通道的活动。咪唑安定通过抑制p38丝裂原活化蛋白激酶抑制凝血酶诱导的心肌细胞热休克蛋白27磷酸化。我们的研究表明，临床使用的局麻药和静脉麻醉药都可以通过调节细胞内信号分子影响离子通道和离子转运蛋白。结果提示，这种作用可能在麻醉作用和痛觉传递中起一定作用。

项目成果

期刊论文数量（67）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Osawa Y, Oda A, Tanahashi S, Iida H, Dohi S: "Effects of Class 1C Antiarrhythmics on Tetrodotoxin-Resistant Na+ Currents in Rat"Anesthesia & Analgesia. 2003(in press). (2004)

Osawa Y、Oda A、Tanahashi S、Iida H、Dohi S：“1C 类抗心律失常药对大鼠河豚毒素抗性 Na 流的影响”麻醉

DOI：
发表时间：
期刊：
影响因子：
0
作者：
通讯作者：

Modulation by the steroid/thyroid hormone superfuamily of TGF-beta-stimlated VEGF release from vascular smooth muscle cells.

类固醇/甲状腺激素超家族对 TGF-β 刺激的血管平滑肌细胞释放 VEGF 的调节。

DOI：
发表时间：
2006
期刊：
J Cell Biochem. Apr 5.(In press)
影响因子：
0
作者：
Tanabe K;Tokuda H;Takai S;Matsushima-Nishiwaki R;Hirade K;Katagiri Y;Dohi S;Kozawa O
通讯作者：
Kozawa O

痛みの評価法と治療効果

疼痛评估方法及治疗效果