1988 Fiscal Year Final Research Report Summary
Development of Molecular Pharmacology in relation to Calcium Binding Proteins
Project/Area Number |
62480117
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Research Category |
Grant-in-Aid for General Scientific Research (B)
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Allocation Type | Single-year Grants |
Research Field |
General pharmacology
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Research Institution | The University of Tokyo |
Principal Investigator |
NONOMURA Yoshiaki The University of Tokyo, Faculty of Medicine, Professor, 医学部, 教授 (80009993)
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Project Period (FY) |
1987 – 1988
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Keywords | Calcium binding protein / Smooth muscle phosphorylation / Inhibitor of phospherylation / Purealin / K-252a / Amilormide / Okadic acid / Reserpine / カルミジェン拮抗薬 |
Research Abstract |
There is calmodulin in smooth muscle as calcium binding protein which is neussary for phosphorylation of myosin light chain. On the other hand, recase of neurotransmitter requires Ca^<2+> and calcium bindmg protein plays an important role of it. Using drugs and factors affecting Ca^<2+> binding proteins, I studied the change of these Ca^<2+> binding proteins and theis function. 1) Puredlin; it was preparad from sea sponge and acted on myosin ATPase for the effect to phosphorylated state. In this study. it acts on calcium calmodulin interaction as an imhibitor. 2) K-252a; it is a kind of bactersal product and antibiotics. This chemicul has an effect to the inhibitory action to smooth muscle myosin light chain kinase at low conuntrations and to calium calmodulin interaction at high concentrations. 3) Amiloride; this diuretic drug inhibits contraction of smooth muscle in intact and skinned state. These effects were dednced from the inhibition of phosphorylation which induced by speiralizad inhibition of light chain kinase. 4) Okadic acid; it was extracted from sea sponge and induced contraction of smooth muscle in free Ca^<2+> and the presence of Ca^<2+> blocker. It acts as an activator of light chain kinase with an inhibitor of phasphatase. 5) Reserpine; it is an activator of actin polymerization and it binds to Go actin. 30KD Ca^<2+> binding protein was purified from bovine cerebellum. Its novel protin may have an impatant role in neurotrausmitlering antion.
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