| Project/Area Number |
06454283
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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 |
Circulatory organs internal medicine
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
KAWAGUCHI Hideaki HOKKAIDO UNIV.MEDICINE PROFESSOR, 医学部, 教授 (70161297)
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| Co-Investigator(Kenkyū-buntansha) |
KITABATAKE Akira HOKKAIDO UNIV.MEDICINE PROFESSOR, 医学部, 教授 (00124769)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 1995: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1994: ¥6,400,000 (Direct Cost: ¥6,400,000)
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| Keywords | G PROTEIN / CARDIOMYOPATHY / CARDIAC FAILURE / beta ADRENERGIC RECEPTOR / DILATED CARDIOMYOPATHY / GENE / beta ADRENERGIC RECEPTOR KINASE (betaARK) |
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| Research Abstract |
G protein serve as transducers between cell surface receptors and intracellular effectors. They consist of three subunits. The desensitization and down-regulation of beta-adrenergic receptor kinase (betaARK). The desensitization and down-regulation of beta-adrenergic receptors (betaAR) have been observed in the heart failure. betaARK is one of the components involved in desensitization of betaAR.G protein betagamma subunit bind betaARK through the pleckstrin homonogy domein. Therefore, we investigated the effects of beta AR stimulation on steady-state level G protein beta subunit (Gbeta) in the rat heart. The whole rat heart was perfused by Langendorff's techniqe with the indicated agents. Immunoblotting using isoform-specific antisera against G protein beta subunits revealed that the rat heart containings at least three G protein beta subunits, beta1, beta2, beta3. The level of Gbeta3 in the cytosol dramatically decreased in the presence of ISO alone or ISO with cGP.Gbeta3 decreased in the presence of EPI as well. Propranolol could blockISO-induced decrease of Gbeta3 in the cytosol. In contrast, the levels of Gbeta1 and Gbeta2 did not change in the presence of ISO or EPI.On the other hand, in membrane fractions the level of Gbeta3 significantly increased in the presence of ISO or EPI.ISO with propranolol or ISO with CGP did not change the level of Gbeta3 in membrane fraction. The levels of Gbeta1 and Gbeta2 did not change in the presence of ISO or EPI in membrane fractions. Taken together, betaAR agonist might induce isoform-specific translocation of Gbeta3 from the cyctosol to the membrane.
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