Involvement of Adenosine in the Antiinflammatory Action of Ketamine

• Julia Mazar

  Postdoctorate Fellow, Department of Nephrology, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel. Department of Chemistry, Bar-Ilan University, Ramat-Gan, Israel.

• Boris Rogachev

  Lecturer.

• Gad Shaked

  Senior Lecturer.

• Nadav Y. Ziv

  Student.

• David Czeiger

  Lecturer, Department of General Surgery B, Soroka University Medical Center.

• Cidio Chaimovitz

  Professor.

• Moshe Zlotnik

  Lecturer.

• Igor Mukmenev

  Technician, Instrumentation Unit, The Institute of Applied Research in Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

• Gerardo Byk

  Associate Professor, Department of Chemistry, Bar-Ilan University, Ramat-Gan, Israel.

• Amos Douvdevani

  Associate Professor, Department of Nephrology.

抄録

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 alpha and interleukin 6 in septic animals. Similarly, adenosine was shown to reduce tumor necrosis factor alpha and mortality of septic animals. The aim of this study was to determine whether adenosine mediates the antiinflammatory effects of ketamine. 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. Ketamine markedly reduced mortality from sepsis, leukocyte recruitment, and tumor necrosis factor-alpha 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 microm) 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 antiinflammatory effects. In contrast, A1 and A3 receptor antagonists had no effect. ZM 241385 reversed the beneficial effect of ketamine on survival from bacterial sepsis. The current data suggest that the sepsis-protective antiinflammatory effects of ketamine are mediated by the release of adenosine acting through the A2A receptor.

収録刊行物

• Anesthesiology

  Anesthesiology 102 (6), 1174-1181, 2005-06-01

  Ovid Technologies (Wolters Kluwer Health)

キーワード

• Anesthesiology and Pain Medicine

詳細情報

• CRID: 1363388845591258496
• NII論文ID: 30009140818
• DOI: 10.1097/00000542-200506000-00017
• ISSN: 00033022
• Web Site: http://pubs.asahq.org/anesthesiology/article-pdf/102/6/1174/359123/0000542-200506000-00017.pdf
• Web Site: http://journals.lww.com/00000542-200506000-00017
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