| Project/Area Number |
04454136
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurophysiology and muscle physiology
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| Research Institution | Nagoya University |
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Principal Investigator |
TAKAI Akira Nagoya University, Dept of Physiology, Associate Professor, 医学部, 助教授 (50126869)
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| Co-Investigator(Kenkyū-buntansha) |
TOKUNO Hiroyuki Nagoya University, Dept of Physiology, Research Associate, 医学部, 助手 (60155520)
TOMITA Tadao Nagoya University, Dept of Physiology, Professor, 医学部, 教授 (50078763)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 1993: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1992: ¥5,200,000 (Direct Cost: ¥5,200,000)
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| Keywords | Smooth muscle / Protein phosphatases / Okadaic acid / Enzyme inhibitor / Protein phosphorylation / Muscle contractility / Neutrophil / Cell motility |
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| Research Abstract |
In mammalian soomth muscles, micromolar concentrations of okadai acid(OA), a potent protien phosphatase ihibitor, produces an irreversible inhibitory effect on the contractility. We observed that this action of OA is accompanied by a significant decrease in myosin light-chain kinase (MLCK) activety, which is partially reversed by treatment of muscle extracts with isolated protein phosphatase 2A.OA many inhibit the activity of smooth muscle MLCK by increasing the phoisphorylation level of MLCK peortein.
In human neutrophils, we examined the effect of OA on the actin assembly caused by various stimulants. OA completely abrogated action assembly induced by phorbol esters, platelet activating factor and leukotriene B4, whereas the effects of the chemotacitic peptide fMLP and opsonized zymosan were unaffected. These results suggest the existence of divergent pathways mediating the resoponse to the neutrophil stimulants.
Using derivatives of OA we examined the relationship between the chemical structure of OA and its affinity to protein phosphatases. We found that modifications of some functional groups of the OA molecule resulted in marked reduction of OA to phosphatases. For example, the affinity to protein dehydrogenation of the 27-hydroxyl group of OA.The marked reduction of affinity, which is equivalent to the deference of 10-15 kJ/mol in standard free energy change, may imply that the 27-hydroxyl group serves as a binding site for the protein phosphatases.
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