Title Polyaspartoyl.L-arginine enhances prostacyclin synthesis in rat aortic endothelial cells
Authors Tang, Zhiyu
Yang, Jian
Liu, Xiaoyan
Wang, Yinye
Peng, Shiqi
Affiliation Peking Univ, Sch Pharmaceut Sci, Dept Mol & Cellular Pharmacol, Beijing 100191, Peoples R China.
Capital Univ Med Sci, Beijing Key Labs Hydrone & Peptides, Beijing 100069, Peoples R China.
Keywords Polyaspartoyl.L-arginine
Nitric oxide
Prostacyclin
Rat aortic endothelial cells
NITRIC-OXIDE SYNTHASE
PLATELET-AGGREGATION
RELEASE
CYCLOOXYGENASE
INHIBITION
ACTIVATION
MECHANISM
CULTURE
ASSAY
Issue Date 2008
Publisher european journal of pharmacology
Citation EUROPEAN JOURNAL OF PHARMACOLOGY.2008,601,(1-3),124-128.
Abstract Nitricoxide (NO) and prostacyclin(PGl(2)) are two of the most important vasodilators produced by endothelial cells, the regulation of NO on PGl(2) production has not been fully clear yet Polyaspartoyl.L-arginine (PDR) is an L-arginine residue-rich compound with inhibitory effects of platelet aggregation and thrombosis. This study investigated its effects on NO production in rat aortic endothelial cells (RAECs) and observed the influence of NO on PGI(2) level in RAECs. NO concentration in the medium of RAECs was assessed with fluorometric method; 6-keto-PGF(1 alpha), the stable metabolite of PGl(2), in the medium of RAECs was measured with radioimmunoassay kits; Protein level of PGl(2) synthase in RAECs was determined by Western blot analysis. PDR (17.0 similar to 170 mu g/ml, equal to 0.5 mu M-5 PM) enhanced NO level in culture medium of RAEC with concentration-dependent manner (P<0.01); L-arginine (170 mu g/ml, equal to 1000 mu M) and 1.70 mu g/ml (0.05 mu M) of PDR slightly increased NO level (P>0.05). Interestingly PDR (1.70-500 mu g/ml), L-arginine (17.0-170 mu g/ml) significantly elevated PGl(2) levels in medium of RAECs (P<0.01), NO synthase inhibitor, N(G)-nitro L-arginine methyl ester (L-NAME), markedly inhibited the elevated PGl(2) levels by PDR and L-arginine. NO donor. sodium nitroprusside(SNP)(1-500 mu M), showed the most powerful effects of increasing PGl(2) level in RAECs, which was not influenced by L-NAME. Cyclooxigenase(COX) inhibitor, indomethacin, significantly reduced elevated PGl(2) level by both PDR and SNP in RAEC medium. PDR (170 mu g/ml) increased the expression of PGl(2) synthase, L-NAME partly inhibited this effect. In conclusion, PDR enhances PGl(2) synthesis in RAEC, which is attributed to its effect of NO production; the stimulating effect of PDR on PGl(2) synthesis may be mediated via COX and PGl(2) synthase. (C) 2008 Published by Elsevier B.V.
URI http://hdl.handle.net/20.500.11897/156839
ISSN 0014-2999
DOI 10.1016/j.ejphar.2008.11.003
Indexed SCI(E)
PubMed
Appears in Collections: 药学院

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