Role of Nitric Oxide in the Change of 5-Hydroxytryptamine Synthesis in the Intestine by a Consecutive Administration of Methotrexate to Rats

被引:5
作者
Machida, Takuji [1 ]
Inotani, Akari [1 ]
Shiga, Saki [1 ]
Kon, Shuto [1 ]
Yanada, Takumi [1 ]
Kobayashi, Hiroya [1 ]
Hamaue, Naoya [2 ]
Hirafuji, Masahiko [1 ]
Iizuka, Kenji [1 ]
机构
[1] Hlth Sci Univ Hokkaido, Sch Pharmaceut Sci, Dept Pharmacol Sci, 1757 Kanazawa, Ishikari, Hokkaido 0610293, Japan
[2] Hlth Sci Univ Hokkaido, Sch Pharmaceut Sci, Dept Mol Biosci, Ishikari, Hokkaido, Japan
关键词
Methotrexate; 5-Hydroxytryptamine; Tryptophan hydroxylase; Substance P; Small intestine; ENTEROCHROMAFFIN CELLS; METABOLISM; TOXICITY; RELEASE; MUCOSA;
D O I
10.1159/000508973
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
This study aimed to investigate whether the consecutive administration of methotrexate affects 5-hydroxytryptamine (5-HT) synthesis in the rat small intestine. Rats received methotrexate at a dose of 12.5 mg/kg intraperitoneally on 4 consecutive days. N-G-nitro-L-arginine methyl ester (L-NAME) was given subcutaneously to inhibit nitric oxide (NO) synthase. Methotrexate moderately altered 5-HT synthesis, whereas the combined administration of methotrexate and L-NAME significantly changed 5-HT synthesis in the rat ileal tissue. These results suggest that endogenous NO has an antagonistic role in the induction of 5-HT synthesis in rats following the consecutive administration of methotrexate.
引用
收藏
页码:723 / 728
页数:6
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