| Project/Area Number |
14571800
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
病態科学系歯学(含放射線系歯学)
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| Research Institution | Tokyo Dental College |
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Principal Investigator |
SAWAKI Kohei TOKYO DENTAL COLLEGE, DEPARTMENT OF DENTISTRY, LECTURER, 歯学部, 講師 (50178828)
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| Co-Investigator(Kenkyū-buntansha) |
OKUBO Migiwa TOKYO DENTAL COLLEGE, DEPARTMENT OF DENTISTRY, ASSISTANT, 歯学部, 助手 (40301519)
KAWAGUCHI Mitsuru TOKYO DENTAL COLLEGE, DEPARTMENT OF DENTISTRY, PROFESSOR, 歯学部, 教授 (20096473)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | salivary secretion / salivary gland / phosphoinositide turnover / intracellular signaling / diazepam / phospholipase C / GTP-binding regulatory protein / イノシトールリン脂質代謝 / 向精神薬 / 耳下腺腺房細胞 / クロライドイオン / ベンゾジアゼピン受容体 / 細胞内カルシウム / ムルカリン受容体 / アドレナリン受容体 |
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| Research Abstract |
Salivary secretion is regulated via intracellular phosphatidylinositide(PI) turnover, which is activated by stimulation of m_3-muscarinic and α_1-adrenergic receptors, GTP-binding regulatory protein(G-protein), and phospholipase C(PLC). Benzodiazepines(BDZs) such as diazepam(DZP) suppress salivary secretion as a serious oral side effect. To elucidate the inhibitory mechanisms of salivary secretion, we investigated the effects of BDZs on the intracellular PI turnover in the salivary glands. In this study, we demonstrated that : (1)DZP dose-dependently inhibited carbachol-stimulated inositol 1,4,5-trisphosphate (IP_3) production in rat parotid cells., ; (2)DZP attenuated the rapid increase in the parotid intracellular Ca^<2+> concentration ([Ca^<2+>]_i) after the stimulation with carbachol. Decrease in [Ca^<2+>]_i was observed in both the presence and absence of extracellular Ca^<2+>. Similar decrease in [Ca^<2+>]_i was also observed when the cells stimulated with phenylephrine. DZP did not induce any detectable change in thapsigargin-stimulated [Ca^<2+>]_i in the parotid cells., ; and (3)Single administration of DZP (5mg/kg, i.p.) did not alter the protein levels of G-protein (G_q type) and PLC (β_3 type) in rat parotid gland, submandibular gland, and brain. Continuous administration of DZP (0.4 or 0.8 mg/kg/day, i.p.) for 10 days decreased PLC levels in the three tissues, but did not alter G-protein levels. Our results suggest that BDZs such as DZP inhibit the intracellular PI turnover in the salivary glands and the decreases in IP_3 and [Ca^<2+>]_i in the salivary gland cells may be connected with the suppression of salivary secretion induced by BDZs.
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