Inhibition of thromboxane A2-induced vasocontraction by KF4939, a new anti-platelet agent, in rabbit mesenteric and dog coronary arteries.
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概要
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The effect of a new anti-platelet agent, KF4939, on thromboxane A<SUB>2</SUB> (TXA<SUB>2</SUB>)-induced vasocontraction was studied in superfused rabbit mesenteric and dog coronary arteries, in comparison with the effects on the contractions evoked by KCI, noradrenaline, serotonin, angiotensin II and histamine. The calcium sources involved in the TXA<SUB>2</SUB>-induced vasocontraction were also examined. The TXA<SUB>2</SUB>-induced contraction of the rabbit mesenteric artery was partly attenuated after exposure to the calcium-free medium, but was not attenuated by nifedipine. The TXA<SUB>2</SUB>-induced contraction of the dog coronary artery was markedly attenuated by nifedipine. These results indicate that TXA<SUB>2</SUB> utilizes both intracellularly stored calcium and an extracellular source of calcium for its vasocontraction, and the voltage-dependent calcium channel plays an important role in the dog coronary artery, but in the rabbit mesenteric artery. KF4939 inhibited the TXA<SUB>2</SUB>-induced contraction in both arteries. In the rabbit mesenteric artery, three times and more higher concentration than that to inhibit TXA<SUB>2</SUB>-induced one were required to inhibit other agonist induced contractions, KF4939 caused no alteration in the KCI-induced contraction of both arteries. Thus, KF4939 seems to be a selective inhibitor of TXA<SUB>2</SUB>-induced vasocontraction, and the receptor-linked mechanism may be a possible site of the TXA<SUB>2</SUB> antagonistic action of KF4939.
- 公益社団法人 日本薬理学会の論文
著者
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Yamada Koji
Deparment Of Food Science And Technology Faculty Of Agriculture Kyushu University
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KUBO Kazuhiro
Department of Cardiovascular Pharmacology, Pharmaceuticals Research Laboratories, Kyowa Hakko Kogyo Co., Ltd.
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SHUTO Katsuichi
Department of Cardiovascular Pharmacology, Pharmaceuticals Research Laboratories, Kyowa Hakko Kogyo Co., Ltd.
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NAKAMIZO Nobuhiro
Department of Cardiovascular Pharmacology, Pharmaceuticals Research Laboratories, Kyowa Hakko Kogyo Co., Ltd.
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YAMADA Koji
Department of Cardiovascular Pharmacology, Pharmaceuticals Research Laboratories, Kyowa Hakko Kogyo Co., Ltd.
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