| Project/Area Number |
03454431
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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 |
Functional basic dentistry
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| Research Institution | The University of Tokushima |
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Principal Investigator |
ISHIDA Hajime The Univ. of Tokushima Sch. of Dentistry ; Professor, 歯学部, 教授 (70028364)
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| Co-Investigator(Kenkyū-buntansha) |
AMANO Ichiro The Univ. of Tokushima Sch. of Dentistry ; Research Associate, 歯学部, 助手 (20212566)
ISHIKAWA Yasuko The Univ. of Tokushima Sch. of Dentistry ; Assistant Professor, 歯学部, 助教授 (40144985)
中西 淳 徳島大学, 歯学部, 助手 (80237320)
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| Project Period (FY) |
1991 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1993: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1992: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1991: ¥4,800,000 (Direct Cost: ¥4,800,000)
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| Keywords | Submandibular glands / Isoproterenol / Mucin secretion / beta-Adrenoceptor / GTP binding proteins / Gi phosphorylation / ADP-ribosylation / Adenylate cyclase / GTP結合蛋白時 / ラット耳下腺 / アミラーゼ分泌の超増感 / アドレナリンβ‐受容体 / Gi蛋白質 / Gs蛋白質 / Protein Kinase A / 唾液腺 / アミラ-ゼ分泌 / Supersensitivity / Desensitization |
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| Research Abstract |
Brief exposure of the tissues to 10muM isoproterenol (IPR) resulted in reduced stimulation of mucin secretion in response to IPR during further incubation coupled with the decrease in the number of beta-adrenoceptors and in the affinity of them for beta-agonist. Treatment of the tissues with IPR caused a 30% decrease in IPR-stimulated adenylate cyclase activity and a 25% increase in the GTP binding capacity of inhibitory GTP binding proteins (Gi proteins). This IPR-treatment triggered a 60% increase in the ability of pertussis toxin (IAP) to catalyze ADP-ribosylation of Gi proteins in the tissue membrane Enhanced function of stimulatory GTP binding proteins (Gs proteins) was observed only during the first incubation of the tissues with IPR.The IAP-catalyzed ADP-ribosylation of Gi proteins in the tissues treated with IPR was decreased by prior treatment with cyclic AMP-dependent protein kinase, but was increased markedly by prior treatment with alkaline phosphatase. The IPR-induced desensitization of j4399 protein secretion and increase in the IAP-catalyzed ADP-ribosylation of Gi proteins were not abserved in the tissues pre-treated with 0.25muM okadaic acid. We also found that GTP binding proteins (G proteins) of molecular weight exists in secretory granule membranes and botulinum toxin has an ability specifically to catalyze ADP-rebosylation of this protein. Release of amylase from the granules was stimulated by ATP or GTPgammaS in the presence of Mg^<2+>. The conformational change in the granules was also caused by these agents, suggesting an importance of the protein in exocytosis.
These results suggest that enzymatic modification of the phosphorylation of Gi proteins is important in the regulation of cell response to subsequent stimulation by adrenergic beta-agonists.
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