Relaxant Effect of Prostaglandin D2–Receptor DP Agonist on Liver Myofibroblast Contraction
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概要
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Increased intrahepatic resistance causes portal hypertension in cirrhosis. Liver myofibroblasts (MFs) are now regarded as the principle cells involved in sinusoidal blood flow regulation. Many other prostaglandin-receptor agonists have been reported to regulate liver MF contraction, but the role of the prostaglandin D2–receptor DP is unknown. In this study, we investigated the effect of a synthetic agonist of prostanoid DP receptor, BW245C, on contractile properties of primary rat liver MFs. Collagen gel contraction assay revealed that BW245C alone (1 and 10 μM) did not induce contraction but induced cell relaxation. Pretreatment with BW245C (10 μM, 30 min) attenuated bradykinin (100 nM)-induced liver MF contraction. Elevation of [Ca2+]i induced by bradykinin (100 nM) was partially suppressed by BW245C pretreatment (10 μM, 3 min). BW245C (1 and 10 μM) significantly increased intracellular cAMP level in a dose-dependent manner. Pretreatment with forskolin (30 – 300 nM, 30 min) and dibutyryl-cAMP (3 – 30 μM, 30 min) significantly reduced bradykinin-induced contraction. Furthermore, a protein kinase A (PKA) inhibitor KT5720 (10 nM to 1 μM, 30 min) blocked the relaxant effect of BW245C. These results suggest that prostanoid DP receptor agonism inhibits bradykinin-induced [Ca2+]i elevation and contraction through cAMP–PKA signal activation in rat liver MFs.
著者
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Murata Takahisa
Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, University
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Hori Masatoshi
Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, University
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Ozaki Hiroshi
Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, University
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Hori Masatoshi
Department Of Radiology Graduate School Of Medicine Osaka University
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Ozaki Hiroshi
Department Of Veterinary Pharmacology Graduate School Of Agriculture And Life Sciences The Universit
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Murata Takahisa
Department Of Veterinary Pharmacology Graduate School Of Agriculture And Life Sciences The Universit
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Maruyama Tomoharu
Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The Univers
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Ayabe Shinya
Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The Univers
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Ozaki Hiroshi
Department Of Electronic Engineering Faculty Of Engineering Osaka University
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Ayabe Shinya
Department Of Veterinary Pharmacology Graduate School Of Agriculture And Life Sciences The Universit
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