Blockade by NIP-142, an Antiarrhythmic Agent, of Carbachol-Induced Atrial Action Potential Shortening and GIRK1/4 Channel

• Matsuda Tomoyuki

  Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences, Japan Biological Research Laboratories, Nissan Chemical Industries, Ltd., Japan

• Ito Mie

  Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences, Japan

• Ishimaru Sayoko

  Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences, Japan

• Tsuruoka Noriko

  Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences, Japan

• Saito Tomoaki

  Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences, Japan

• Iida-Tanaka Naoko

  Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences, Japan Department of Food Science, Otsuma Woman’s University, Japan

• Hashimoto Norio

  Biological Research Laboratories, Nissan Chemical Industries, Ltd., Japan

• Yamashita Toru

  Biological Research Laboratories, Nissan Chemical Industries, Ltd., Japan

• Tsuruzoe Nobutomo

  Biological Research Laboratories, Nissan Chemical Industries, Ltd., Japan

• Tanaka Hikaru

  Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences, Japan

• Shigenobu Koki

  Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences, Japan

Abstract

Mechanisms for the atria-specific action potential-prolonging action of NIP-142 ((3R*,4S*)-4-cyclopropylamino-3,4-dihydro-2,2-dimethyl-6-(4-methoxyphenylacetylamino)-7-nitro-2H-1-benzopyran-3-ol), a benzopyran compound that terminates experimental atrial arrhythmia, was examined. In isolated guinea-pig atrial tissue, NIP-142 reversed the shortening of action potential duration induced by either carbachol or adenosine. These effects were mimicked by tertiapin, but not by E-4031. NIP-142 concentration-dependently blocked the human G protein-coupled inwardly rectifying potassium channel current (GIRK1/4 channel current) expressed in HEK-293 cells with an EC₅₀ value of 0.64 μM. At higher concentrations, NIP-142 blocked the human ether a go-go related gene (HERG) channel current with an EC₅₀ value of 44 μM. In isolated guinea-pig papillary muscles, NIP-142 had no effect on the negative inotropic effect of carbachol under β-adrenergic stimulation, indicating lack of effect on the muscarinic receptor and Gi protein. These results suggest that NIP-142 directly inhibits the acetylcholine-activated potassium current.<br>

Journal

• Journal of Pharmacological Sciences

  Journal of Pharmacological Sciences 101 (4), 303-310, 2006

  The Japanese Pharmacological Society

Keywords

• NIP-142
• antiarrhythmic agent
• action potential duration
• GIRK1/4 channel
• atrial fibrillation

Details

• CRID: 1390282680154396288
• NII Article ID: 10018236475
• NII Book ID: AA11806667
• DOI: 10.1254/jphs.fp0060324
• ISSN: 13478648
• ISSN: 13478613
• NDL BIB ID: 8023029
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I8023029
• Web Site: https://search.jamas.or.jp/link/ui/2007132382
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
• Abstract License Flag: Disallowed