INHIBITORY EFFECT OF INDOMETHACIN ON NEONATAL LUNG CATABOLISM OF PROSTAGLANDIN E_2: POSSIBLE MECHANISM OF THE RE-OPENING OF THE DUCTUS ARTERIOSUS AFTER INDOMETHACIN THERAPY
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概要
- 論文の詳細を見る
Indomethacin has been used to treat patent ductus arteriosus (PDA). Re-opening of the ductus arteriosus (DA) after indomethacin therapy, however, is common, although the reason is unclear. Patency of the ductus arteriosus is thought to be maintained primarily by the vasodilatory effect of PGE_2 in fetuses and nenonates. The enzyme, 15-hydroxy prostaglandin dehydrogenase (15-PGDH) catalyzes the initial reactions converting the biologically active PGE_2 to its inactive metabolite 15-keto-PGE_2, and the lungs are a major site of this inactivation. In the present study, the effect of prenatal indomethacin treatment on the activity of neonatal rat lung 15-PGDH, and the effect of prenatal indomethacin on the re-opening of the DA induced by PGE_2 were examined in rats. Indomethacin treatment at 3 mg/kg/day from day 18 to day 20 of gestation significantly decreased the activity of 15-PGDH in neonatal lungs. In a subsequent experiment, subcutaneous injection of PGE_2 (4 μg) was given to newborn rats 3hr after Cesarean delivery from pregnant females administered indomethacin (1, 3 mg/kg/day) as in the above experiment. The ratio of the DA to pulmonary artery was determined at intervals after injection. Maternal indomethacin treatment significantly increased the re-opening of the DA and prolonged the duration of re-opening induced by PGE_2. These results suggest that the decrease in the catabolism of PGE_2 in the lung is partly responsible for the failure of indomethacin therapy for PDA.
- 日本トキシコロジー学会の論文
- 1996-11-25
著者
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AKAHORI Fumiaki
Department of Veterinary Pharmacology, School of Veterinary Medicine, Azabu University
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ARISHIMA Kazuyoshi
Department of Anatomy II School of Veterinary Medicine, Azabu University
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YAMAMOTO Masako
Department of Anatomy II School of Veterinary Medicine, Azabu University
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Takagi Hironori
Toxicology Laboratory Drug Metabolism And Toxicology Research Center Taisho Pharmaceutical Co. Ltd.
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TAKIZAWA Tatsuya
Departments of Developmental Biotechnology, Azabu University, School of Veterinary Medicine
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IKEDA Yoshinori
Departments of Developmental Biotechnology, Azabu University, School of Veterinary Medicine
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TOGASHI Hirofumi
Department of Anatomy II, Azabu University, School of Veterinary Medicine
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MASAOKA Toshio
Departments of Pharmacology, Azabu University, School of Veterinary Medicine
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Masaoka T
School Of Veterinary Medicine Azabu University
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Masaoka Toshio
Department Of Comparative Toxicology School Of Veterinary Medicine Azabu University
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Akahori F
School Of Veterinary Medicine Azabu University
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Akahori Fumiaki
麻布大学 獣医学部実験動物学
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Akahori Fumiaki
Department Of Veterinary Pharmacology School Of Veterinary Medicine Azabu University Sagamihara
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Akahori Fumiaki
School Of Veterinary Medicine Azabu University
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Akahori Fumiaki
Department Of Environmental Health Jichi Medical School : National Institute Of Industrial Health :
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Yamamoto Masako
Department Of Anatomy Ii School Of Veterinary Medicine Azabu University
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Arishima Kazuyoshi
Department Of Anatomy Ii School Of Veterinary Medicine Azabu University
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Arishima Kazuyoshi
Department Of Veterinary Anatomy Ii Azabu University School Of Veterinary Medicine
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Arishima Kazuyoshi
Anatomy Ii School Of Veterinary Medicine Azabu University
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Arishima Kazuyoshi
Department Of Anatomy Ii Azabu University School Of Veterinary Medicine
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Yamamoto Masaru
Laboratories Of Natural Information Science Graduate School Of Integrated Science Yokohama City Univ
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Takagi H
Toxicology Laboratory Drug Metabolism And Toxicology Research Center Taisho Pharmaceutical Co. Ltd.
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Togashi H
Department Of Cardiovascular Medicine Hokkaido University Graduate School Of Medicine
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Ikeda Yoshinori
Department Of Materials Science And Engineering Tokyo Institute Of Technology
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Yamamoto Masaru
Laboratories Of Natural Information Science Graduate School Of Integrated Science Yokohama City Univ
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Yamamoto Masako
Department Of Anatomy Ii Azabu University School Of Veterinary Medicine
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Yamamoto Masahiro
Center For Kampo Medicine Keio University School Of Medicine
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Togashi H
Department Of Anatomy Ii Azabu University School Of Veterinary Medicine
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Ikeda Yoshinori
Department of Developmental Biotechnology, Azabu University School of Veterinary Medicine
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ARISHIMA Kazuyoshi
Department of Anatomy II
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Togashi Hirofumi
Department of Anatomy II, Azabu University School of Veterinary Medicine
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TAKIZAWA Tatsuya
Departments of Developmental and Reproductive Biotechnology, Azabu University School of Veterinary Medicine, Fuchinobe, Sagamihara-shi, Kanagawa 229-8501, Japan
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