Doxorubicin Affects the Cardiac Muscarinic System in the Rat.

• CHUGUN Akihito

  Department of Veterinary Pharmacology, School of Veterinary Medicine and Animal Sciences, Kitasato University

• UCHIDE Tsuyoshi

  Department of Toxicology, School of Veterinary Medicine and Animal Sciences, Kitasato University

• TEMMA Kyosuke

  Department of Toxicology, School of Veterinary Medicine and Animal Sciences, Kitasato University

• KENNEDY Richard H.

  Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences

• KLIMBERG Suzanne V.

  Department of Surgery, University of Arkansas for Medical Sciences

• HARA Yukio

  Department of Veterinary Pharmacology, School of Veterinary Medicine and Animal Sciences, Kitasato University

• SASAKI Takushi

  Department of Toxicology, School of Veterinary Medicine and Animal Sciences, Kitasato University

• AKERA Tai

  Merck Sharp and Dohm Research Laboratories Japan

抄録

During the study on the mechanism of doxorubicin-induced cardiotoxicity, we observed that a long incubation (4 hr) with doxorubicin reduced the maximal negative inotropic effects of a muscarinic receptor agonist, carbachol. The mechanism responsible for this doxorubicin-induced reduction of the efficacy of carbachol was examined in isolated guinea pig hearts. In isolated left atrial muscle preparations, 1 hr incubation with 100 μM doxorubicin caused a parallel right-ward shift of the concentration-response curves for carbachol, but a longer (4 hr) incubation with this agent (30, 100 or 200 μM), caused a significant reduction of the magnitude of the negative inotropic effect of carbachol in addition to the concentration-dependent parallel right-ward shift. The 4-hr incubation with these concentrations of doxorubicin also reduced the maximal negative inotropic effect of an adenosine A₁ receptor agonist, R-phenylisopropyl adenosine (R-PIA), without affecting the potency of this agonist. Doxorubicin (1 to 100 μM) reduced [³H]quinuclidinyl benzilate (QNB) binding in a concentration dependent manner, but failed to alter [³H]R-PIA binding. The decrease in the magnitude of the maximal negative inotropic effect by doxorubicin was caused by changes in the muscarinic system at steps common to the transduction of muscarinic and adenosine A₁ receptor mechanisms.

収録刊行物

• Ｔｈｅ　Ｊｏｕｒｎａｌ　ｏｆ　Ｖｅｔｅｒｉｎａｒｙ　Ｍｅｄｉｃａｌ　Ｓｃｉｅｎｃｅ

  Ｔｈｅ　Ｊｏｕｒｎａｌ　ｏｆ　Ｖｅｔｅｒｉｎａｒｙ　Ｍｅｄｉｃａｌ　Ｓｃｉｅｎｃｅ 63 (12), 1315-1322, 2001

  公益社団法人 日本獣医学会

キーワード

• adenosine receptor
• cardiotoxicity
• doxorubicin
• muscarinic receptor
• rat heart

詳細情報

• CRID: 1390001206425723008
• NII論文ID: 110003920796
• NII書誌ID: AA10796138
• DOI: 10.1292/jvms.63.1315
• COI: 1:CAS:528:DC%2BD38XlvFGitQ%3D%3D
• ISSN: 13477439
• ISSN: 09167250
• NDL書誌ID: 6016929
• PubMed: 11789610
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I6016929
• Web Site: http://www.jstage.jst.go.jp/article/jvms/63/12/63_12_1315/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2002118255
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可