Anticholinergic Effects of Artemisinin, an Antimalarial Drug, in Isolated Guinea Pig Heart Preparations
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概要
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Concern has been growing about the cardiac toxicity of antimalarial drugs. Artemisinin, a unique type of antimalarial drug originating from a Chinese medicinal plant, has minimal adverse effects, but it has been reported to inhibit delayed rectifier potassium current, a voltage-gated potassium current. However, no studies have been published concerning the effect of artemisinin on ligand-gated potassium currents. Therefore, in the present study, we examined the influence of artemisinin on the acetylcholine receptor-operated potassium current (IK.ACh), a ligand-gated potassium current, in guinea pig atrial myocytes using a patch clamp technique. Artemisinin (1 to 300 μM) inhibited IK.ACh induced by extracellular application of both carbachol (1 μM) and adenosine (10 μM) and that induced by intracellular loading of GTPγS (100 μM) in a concentration-dependent manner. Artemisinin inhibited carbachol-induced, adenosine-induced, and GTPγS-activated IK.ACh within almost the same concentration range. In left atria, artemisinin (1 to 100 μM) partially reversed the shortening of action potential duration induced by carbachol in a concentration-dependent manner. Carbachol-induced negative inotropic action in left atria was also inhibited by artemisinin (10 to 300 μM). In conclusion, we suggest that the anticholinergic action of artemisinin is mediated through inhibition of IK.ACh via inhibition of the muscarinic potassium channel and/or associated GTP-binding proteins.
- 公益社団法人 日本獣医学会の論文
著者
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Hara Yukio
Laboratory Of Veterinary Pharmacology School Of Veterinary Medicine Kitasato University
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Kizaki Keiichiro
Laboratory Of Reproductive Biology And Technology Depar
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YAMAWAKI Hideyuki
Laboratory of Veterinary Pharmacology, Kitasato University, Towada, Aomori 034–8628, Japan
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YAMAWAKI Hideyuki
Laboratory of Veterinary Pharmacology, School of Veterinary Medicine and Animal Sciences, Kitasato University
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SHIMADA Masami
Laboratory of Veterinary Pharmacology, School of Veterinary Medicine and Animal Sciences, Kitasato University
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OKADA Kiyohiro
Laboratory of Veterinary Pharmacology, School of Veterinary Medicine and Animal Sciences, Kitasato University
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TANAI Toshiki
Laboratory of Veterinary Pharmacology, School of Veterinary Medicine and Animal Sciences, Kitasato University
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ICHIKAWA Daiki
Laboratory of Veterinary Pharmacology, School of Veterinary Medicine and Animal Sciences, Kitasato University
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MIYAKE Kimihito
Laboratory of Veterinary Pharmacology, School of Veterinary Medicine and Animal Sciences, Kitasato University
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