Antagonism of Platelet-Activating Factor-Induced Increase in Cytosolic Free Calcium Concentration in Human Endothelial Cells.
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概要
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The effects of platelet-activating factor (PAF) antagonists on the agonist-induced increase in cytosolic free calcium concentration, [Ca<SUP>2+</SUP>]<SUB>i</SUB>, in human vascular endothelial cells grown in monolayer were investigated by a continuous superfusion technique using a calcium fluorescent probe, fura-2. PAF caused a small but dose-dependent increase in [Ca<SUP>2+</SUP>]<SUB>i</SUB>. Seven structurally dissimilar PAF antagonists dose-dependently suppressed the peak response, among which WEB 2086 was the most potent, followed by WEB 2170 > FR 900452 ≈ ONO 6240 > BN 52021 ≈ kad-surenone ≈ CV 3988. These antagonists except for CV 3988 were specific for PAF, since they had no effects on calcium mobilization induced by thrombin or histamine, while CV 3988 had a non-specific effect. PAF in the same range of concentration increased prostacyclin release from human endothelial cells. WEB 2086 also inhibited the PAF-induced prostacyclin release, while it had no effect on the release induced by histamine and thrombin. These results demonstrate the specificity and dose-response characteristics of PAF antagonists in cultured human endothelial cells and suggest that a PAF antagonist could be a valuable therapeutic agent in certain human diseases where PAF activation of endothelial cells may have a critical role.
- 公益社団法人 日本薬理学会の論文
著者
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Hirafuji Masahiko
Department Of Pharmacology Faculty Of Pharmaceutical Sciences Health Sciences University Of Hokhaido
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Shinoda Hisashi
Department Of Applied Dental Pharmacology Tohoku University Graduate School Of Dentistry
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Hirafuji Masahiko
Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido
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- Antagonism of Platelet-Activating Factor-Induced Increase in Cytosolic Free Calcium Concentration in Human Endothelial Cells.
- Foreword
- Inhibition of prostaglandin I2 biosynthesis in rat dental pulp by phenolic dental medicaments.