Carboxy-PTIO Increases the Tetrahydrobiopterin Level in Mouse Brain Microvascular Endothelial Cells
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概要
- 論文の詳細を見る
The aim of the present study was to characterize the increase in tetrahydrobiopterin (BH4), which is a cofactor for nitric oxide synthase (NOS), by carboxy-PTIO, a scavenger of nitric oxide (NO), in vascular endothelial cells. BH4 level was determined by oxidation under acidic conditions as biopterin. Addition of lipopolysaccharide (LPS) to endothelial cells increased mRNA levels of inducible NOS (iNOS) and GTP-cyclohydrolase I (GTPCH), which is a rate-limiting enzyme for BH4 synthesis, and the biopterin level. NOS inhibitors, NO-donors and <sc>L</sc>-arginine, a substrate of NOS, did not affect the increase in the biopterin level induced by LPS, suggesting that BH4 synthesis is unlikely to be modulated by NO produced by iNOS during LPS treatment. However, carboxy-PTIO increased the biopterin level in the absence and the presence of LPS. Carboxy-PTIO did not affect the expression of GTPCH mRNA level. Moreover, 2,4-diamino-6-hydroxypyrimidine, an inhibitor of GTPCH, inhibited only about 30% of the carboxy-PTIO-induced increase in the biopterin level. Whereas, N-acetylserotonin, an inhibitor of sepiapterin reductase, strongly inhibited the increase in biopterin level. Carboxy-PTIO inhibited the accumulation of pterin, a decomposition product of BH4 in endothelial cells. These findings suggest that carboxy-PTIO accumulates BH4 under basal and LPS-treated conditions in vascular endothelial cells due to both inhibition of the decomposition of BH4 to pterin and activation of the salvage pathway of BH4 synthesis via sepiapterin reductase.
- 社団法人 日本薬理学会の論文
- 2001-09-01
著者
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Yamamoto Toshinori
昭和大学 医学部第2外科
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Ishii Masakazu
Department Of Pathophysiology School Of Pharmacy Showa University
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Ishii Masakazu
Center For Integrative Bioscience Okazaki National Research Institutes
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SHIMIZU Shunichi
Department of Pathophysiology, School of Pharmaceutical Sciences, Showa University
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KIUCHI Yuji
Department of Pathophysiology, School of Pharmaceutical Sciences, Showa University
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Yamamoto Toshinori
Clinical Pharmacy School Of Pharmaceutical Sciences Showa University
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Yamamoto T
Okayama Univ. Medical School Okayama Jpn
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ISHII Masakazu
Clinical Pharmacy, School of Pharmaceutical Sciences, Showa University
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IWASAKI Michiko
Departments of Pathophysiology, School of Pharmaceutical Sciences, Showa University
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SHIOTA Kazuhiro
Departments of Pathophysiology, School of Pharmaceutical Sciences, Showa University
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Kiuchi Yuji
Center Of Pharmaceutical Education School Of Pharmacy Showa Univ.
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Kiuchi Y
Department Of Electronic Engineering Faculty Of Technology Tokyo University Of Agriculture And Techn
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Kiuchi Yuji
Department Of Electronic Engineering Faculty Of Technology Tokyo University Of Agriculture And Techn
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Iwasaki Michiko
Departments Of Pathophysiology School Of Pharmaceutical Sciences Showa University
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Shiota Kazuhiro
Departments Of Pathophysiology School Of Pharmaceutical Sciences Showa University
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Yamamoto Toshinori
Department Of Clinical Pharmacy Showa University School Of Pharmaceutical Sciences
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Shimizu Shunichi
Dep. Of Pathophysiology School Of Pharmacy Showa Univ.
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Iwasaki Michiko
Department Of Gastroenterology And Hepatology Graduate School Tokyo Medical And Dental University
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Shiota Kazuhiro
Department of Pathophysiology, School of Pharmaceutical Sciences, Showa University
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