1990 Fiscal Year Final Research Report Summary
Role of Inositol Polyphosphates in Ca^<2+> Homeostasis
Project/Area Number |
01570139
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Research Category |
Grant-in-Aid for General Scientific Research (C)
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Allocation Type | Single-year Grants |
Research Field |
General medical chemistry
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Research Institution | Kyushu University |
Principal Investigator |
HIRATA Masato Kyushu University. Faculty of Dentistry. Associate Professor, 歯学部, 助教授 (60136471)
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Project Period (FY) |
1989 – 1990
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Keywords | IP_3 analogs / IP_3 phosphatase / IP_3 kinase / IP_3 receptor / Ca^<2+> ion / IP_3 affinity column |
Research Abstract |
A series of inositol 1.4.5-trisphosphate (IP_3) analogs, with a bulky substituent on the 2nd carbon of the inositol ring, has been synthesized and examined to explore the structure-activity relationships among IP_3-5-phosphatase. IP_3-3-kinase, and IP_3 binding protein. All analogs (racemic mixtures) inhibited the hydrolysis of [^3H] IP_3 catalyzed by erythrocyte ghosts. With a lower Ki value than seen with IP_3. The effective enantiomer in this process was found to be L-type. The analogs were capable of inhibiting the phosphorylation of [^3H] IP_3 to [^3H] IP_4 by brain cytosol. Although higher concentrations than IP_3 were required. By lowering free Ca^<2+>, the concentrations required for the inhibition became low. In this reaction. the D-enantiomer was effective. The D-enantiomer of these compoundsalso inhibited the binding of [^3H] IP_3 to cerebellum microsomes, With the same potency as seen with IP_3. And they acted as a full agonists in releasing Ca^<2+> from permeabilized macrophages. These results indicate that the 2nd position of IP_3 can be modified with only minor reduction in potency in several assay systems. Thus, the IP_3 analogs synthesized here may be linked to other molecules without loss of their biological activities. For example, the IP_3 analogs were coupled with Sepharose 4B to make IP_3 affinity columns, and the columns were proved to be useful for purifying the IP_3-recognizing proteins.
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[Publications] Hirata,M.,Watanabe,Y.,Ishimatsu,T.,Ikebe,T.,Kimura,Y.,Yamaguchi,K.,Ozaki,S.,Koga,T.: "Synthetic inositol trisphosphate analogs and their effects on Phosphase,kinase,and the release of Ca^<2+>." J.Biol.Chem.264. 20303-20308 (1989)
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「研究成果報告書概要(和文)」より
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[Publications] HiratA,M.,Watanabe,Y.,Ishimatsu,T.,Yanaga,F.,Koga,T.: "Inositol 1,4,5ーtrisphosphate affinity chromatography." Biochem.Biophys.Res.Commun.168. 379-386 (1990)
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「研究成果報告書概要(和文)」より
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[Publications] Hirata,M.,Yanaga,F.,Koga,T.,Ogasawara,T.,Watanabe,Y.,Ozaki S.: "Stereospecific recognition of inositol 1,4,5ーtrisphosphate analogs by the phosphatase,kinase,and binding proteins." J.Biol.Chem.265. 8404-8407 (1990)
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「研究成果報告書概要(和文)」より
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[Publications] Kimura,Y.,Watanabe,Y.,Ozaki,S.,Koga,T.,Hirata,M.: "Ca^<2+>/calmodulin independent inositol 1,4,5ーtrisphosphate 3ーkinase activity in guinea pig peritoneal macrophages." Comp.Biochem.Physiol.97B. 527-533 (1990)
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「研究成果報告書概要(和文)」より
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[Publications] Hirata,M.,Kimura,Y.,Ishimatsu,T.,Yanaga,F.,Shuto,T.,Sasaguri,T.,Koga,T.,Watanabe,Y.,Ozaki,S.: "Synthetic inositol 1,3,4,5ーtetrakisphosphate analogs." Biochem.J.
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[Publications] Masato Hirata, Yuichi Kimura, Toyohiro Ishimatsu, Fumi Yanaga, Toshihide Shuto, Toshiyuki Sasaguri, Toshitaka Koga, Yutaka Watanabe, and Shoichiro Ozaki: "Synthetic inositol 1, 3, 4, 5-tetrakisphosphate analogs." Biochem. J.
Description
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