Involvement of adenosine in the antiinflammatory action of ketamine
Involvement of adenosine in the antiinflammatory action of ketamine
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DOI：
10.1097/00000542-200506000-00017
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发表时间：
2005-06-01
期刊：
影响因子：
8.8
通讯作者：
Douvdevani, A
中科院分区：
文献类型：
--
作者：
Mazar, J;Rogachev, B;Douvdevani, A
背景：氯胺酮是一种麻醉药。亚麻醉剂量的氯胺酮已被证明可以降低手术后白细胞介素-6的浓度，并减少败血症动物的死亡率和肿瘤坏死因子a和白细胞介素-6的产生。类似地，腺苷显示出降低肿瘤坏死因子a和败血症动物的死亡率。本研究的目的是确定腺苷是否介导ketamine.Methods的抗炎作用：脓毒症诱导小鼠的脂多糖或大肠杆菌接种。白细胞募集和细胞因子浓度用作炎症标志物。腺苷浓度进行了测定，通过高效液相色谱法，并参与氯胺酮的腺苷的影响证明了腺苷受体激动剂和拮抗剂。结果：氯胺酮显着降低死亡率败血症，白细胞招募，肿瘤坏死因子-a和白细胞介素-6的浓度。小鼠和大鼠的氯胺酮给药与血清（高达5 μ m）和腹腔液中腺苷在20-35分钟时的激增有关。腺苷A2 A受体激动剂CGS-21680模拟氯胺酮在腹膜炎中的作用，而A2 A受体拮抗剂DMPX和ZM 241385阻断其抗炎作用。相反，A1和A3受体拮抗剂没有效果。ZM 241385逆转氯胺酮对细菌sepsis.Conclusions生存的有益作用：目前的数据表明，氯胺酮的脓毒症保护抗炎作用是通过A2 A受体作用的腺苷释放介导的。
Background: Ketamine is an anesthetic drug. Subanesthetic doses of ketamine have been shown to reduce interleukin-6 concentrations after surgery and to reduce mortality and the production of tumor necrosis factor a and interleukin 6 in septic animals. Similarly, adenosine was shown to reduce tumor necrosis factor a and mortality of septic animals. The aim of this study was to determine whether adenosine mediates the antinflammatory effects of ketamine.Methods: Sepsis was induced in mice by lipopolysaccharide or Escherichia coli inoculation. Leukocyte recruitment and cytokine concentrations were used as inflammation markers. Adenosine concentrations were assayed by high-performance liquid chromatography, and the involvement of adenosine in the effects of ketamine was demonstrated by adenosine receptor agonists and antagonists.Results: Ketamine markedly reduced mortality from sepsis, leukocyte recruitment, and tumor necrosis factor-a and interleukin-6 concentrations. Ketamine administration in mice and rats was associated with a surge at 20-35 min of adenosine in serum (up to 5 mu m) and peritoneal fluid. The adenosine A2A receptor agonist CGS-21680 mimicked the effect of ketamine in peritonitis, whereas the A2A receptor antagonists DMPX and ZM 241385 blocked its antinflammatory effects. In contrast, A1 and A3 receptor antagonists had no effect. ZM 241385 reversed the beneficial effect of ketamine on survival from bacterial sepsis.Conclusions: The current data suggest that the sepsis-protective antinflammatory effects of ketamine are mediated by the release of adenosine acting through the A2A receptor.