Synthetic inositol trisphosphate analogs and their effects on phosphatase, kinase, and the release of Ca 2+

Masato Hirata, Y. Watanabe, T. Ishimatsu, T. Ikebe, Y. Kimura, K. Yamaguchi, S. Ozaki, T. Koga

研究成果: ジャーナルへの寄稿記事

83 引用 (Scopus)

抄録

A series of inositol 1,4,5-trisphosphate (IP 3 ) analogs and positional isomers was examined to explore the structure-activity relationships among IP 3 5-phosphatase, IP 3 3-kinase, and the release of Ca 2+ . All analogs with additional groups on the 2nd position of IP 3 inhibited the hydrolysis of [5- 32 P]IP 2 catalyzed by erythrocyte ghosts, with a lower K(i) value than seen with IP 3 . IP 3 dehydroxylated at the 2nd position also had a lower K(i), while 2,4,5-IP 3 or cyclic (1:2),4,5-IP 3 had higher K(i) values. Among these compounds 2-deoxy-IP 3 was as potent as IP 3 in inhibiting the phosphorylation by [ 3 H] IP 3 -3-kinase in rat brain cytosol. The other compounds, except for 2,4,5-IP 3 inhibited the phosphorylation, however, 2-30 times higher concentrations were required. By lowering free Ca 2+ , the concentrations required for half-maximal inhibition were low, while those of IP 3 , 2-deoxy-IP 3 , and positional isomers remained unchanged. These compounds acted as full agonists in releasing Ca 2+ from permeabilized macrophages, although 1.6-50-fold higher concentrations than IP 3 were required. These compounds also inhibited the binding of [ 3 H]IP 3 to rat cerebellum and bovine adrenal cortex microsomes, but the potencies were 2.9-33 times less than that of IP 3 . Thus, the 2nd position of IP 3 can be modified with only a slight loss of biological activity.

元の言語英語
ページ(範囲)20303-20308
ページ数6
ジャーナルJournal of Biological Chemistry
264
発行部数34
出版物ステータス出版済み - 12 20 1989

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Inositol
Phosphoric Monoester Hydrolases
Phosphorylation
Phosphotransferases
Isomers
Rats
Inositol 1,4,5-Trisphosphate
Macrophages
Adrenal Cortex
Erythrocyte Membrane
Structure-Activity Relationship
Microsomes
Bioactivity
Cytosol
Cerebellum
Hydrolysis
Brain
inositol 2,4,5-trisphosphate

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

これを引用

Hirata, M., Watanabe, Y., Ishimatsu, T., Ikebe, T., Kimura, Y., Yamaguchi, K., ... Koga, T. (1989). Synthetic inositol trisphosphate analogs and their effects on phosphatase, kinase, and the release of Ca 2+ Journal of Biological Chemistry, 264(34), 20303-20308.

Synthetic inositol trisphosphate analogs and their effects on phosphatase, kinase, and the release of Ca 2+ . / Hirata, Masato; Watanabe, Y.; Ishimatsu, T.; Ikebe, T.; Kimura, Y.; Yamaguchi, K.; Ozaki, S.; Koga, T.

:: Journal of Biological Chemistry, 巻 264, 番号 34, 20.12.1989, p. 20303-20308.

研究成果: ジャーナルへの寄稿記事

Hirata, M, Watanabe, Y, Ishimatsu, T, Ikebe, T, Kimura, Y, Yamaguchi, K, Ozaki, S & Koga, T 1989, ' Synthetic inositol trisphosphate analogs and their effects on phosphatase, kinase, and the release of Ca 2+ ', Journal of Biological Chemistry, 巻. 264, 番号 34, pp. 20303-20308.
Hirata M, Watanabe Y, Ishimatsu T, Ikebe T, Kimura Y, Yamaguchi K その他. Synthetic inositol trisphosphate analogs and their effects on phosphatase, kinase, and the release of Ca 2+ Journal of Biological Chemistry. 1989 12 20;264(34):20303-20308.
Hirata, Masato ; Watanabe, Y. ; Ishimatsu, T. ; Ikebe, T. ; Kimura, Y. ; Yamaguchi, K. ; Ozaki, S. ; Koga, T. / Synthetic inositol trisphosphate analogs and their effects on phosphatase, kinase, and the release of Ca 2+ :: Journal of Biological Chemistry. 1989 ; 巻 264, 番号 34. pp. 20303-20308.
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abstract = "A series of inositol 1,4,5-trisphosphate (IP 3 ) analogs and positional isomers was examined to explore the structure-activity relationships among IP 3 5-phosphatase, IP 3 3-kinase, and the release of Ca 2+ . All analogs with additional groups on the 2nd position of IP 3 inhibited the hydrolysis of [5- 32 P]IP 2 catalyzed by erythrocyte ghosts, with a lower K(i) value than seen with IP 3 . IP 3 dehydroxylated at the 2nd position also had a lower K(i), while 2,4,5-IP 3 or cyclic (1:2),4,5-IP 3 had higher K(i) values. Among these compounds 2-deoxy-IP 3 was as potent as IP 3 in inhibiting the phosphorylation by [ 3 H] IP 3 -3-kinase in rat brain cytosol. The other compounds, except for 2,4,5-IP 3 inhibited the phosphorylation, however, 2-30 times higher concentrations were required. By lowering free Ca 2+ , the concentrations required for half-maximal inhibition were low, while those of IP 3 , 2-deoxy-IP 3 , and positional isomers remained unchanged. These compounds acted as full agonists in releasing Ca 2+ from permeabilized macrophages, although 1.6-50-fold higher concentrations than IP 3 were required. These compounds also inhibited the binding of [ 3 H]IP 3 to rat cerebellum and bovine adrenal cortex microsomes, but the potencies were 2.9-33 times less than that of IP 3 . Thus, the 2nd position of IP 3 can be modified with only a slight loss of biological activity.",
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AU - Hirata, Masato

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AU - Ikebe, T.

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