文章基本信息

标题：Carnosine Facilitates Nitric Oxide Production in Endothelial F-2 Cells
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作者：Satoru Takahashi ; Yukiko Nakashima ; Ken-ichi Toda 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2009
卷号：32
期号：11
页码：1836-1839
DOI：10.1248/bpb.32.1836
出版社：The Pharmaceutical Society of Japan
摘要：We examined the effect of carnosine (β-alanyl-histidine) on nitric oxide (NO) production and endothelial NO synthase (eNOS) activation in endothelial F-2 cells. Carnosine enhanced NO production in a dose-dependent manner, and the stimulatory effect of carnosine was observed at concentrations exceeding 5 m M . The carnosine-stimulated NO production was inhibited by N ^G-nitro- L -arginine methyl ester, but not by N ^G-nitro- D -arginine methyl ester. In contrast, β-alanine, histidine (carnosine components) and anserine ( N -methyl carnosine) failed to increase NO production. Carnosine had no effect on NO production for the initial 5 min, but thereafter resulted in a gradual increase in NO production up to 15 min. Carnosine did not induce phosphorylation of eNOS at Ser1177. The carnosine-induced increase in NO production was observed even when extracellular Ca²⁺ was depleted by ethylene glycol bis(2-aminoethyl ether)- N , N , N ′- N ′-tetraacetic acid however, the effect was abolished upon depletion of intracellular Ca²⁺ by BAPTA. After F-2 cells were incubated with carnosine for 4 min, intracellular Ca²⁺ concentration gradually increased. The carnosine-induced increase in intracellular Ca²⁺ concentration occurred even in the absence of extracellular Ca²⁺. These results indicate that carnosine facilitates NO production in endothelial F-2 cells. It is also suggested that eNOS is activated by Ca²⁺, which might be released from intracellular Ca²⁺ stores in response to carnosine.
关键词：carnosine;endothelial cell;nitric oxide;endothelial nitric oxide synthase;intracellular Ca2+