Project/Area Number |
09671906
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Functional basic dentistry
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Research Institution | NIHON UNIVERSITY SCHOOL OF DENTISTRY AT MATSUDO |
Principal Investigator |
SUGIYA Hiroshi NIHON UNIVERSITY SCHOOL OF DENTISTRY AT MATSUDO,DEPARTMENT OF PHYSIOLOGY,ASSOCIATE PROFESSOR, 松戸歯学部, 助教授 (20050114)
|
Co-Investigator(Kenkyū-buntansha) |
YOSHIGAKI Junko NIHON UNIVERSITY SCHOOL OF DENTISTRY AT MATSUDO,DEPARTMENT OF PHYSIOLOGY RESEARC, 松戸歯学部, 助手 (40256904)
|
Project Period (FY) |
1997 – 1998
|
Project Status |
Completed (Fiscal Year 1998)
|
Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1997: ¥1,600,000 (Direct Cost: ¥1,600,000)
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Keywords | SALIVARY GLANDS / EXOCYTOSIS / CALCIUM / SUBLINGUAL GLAND / CYCLIC GMP / NITRIC OXIDE / ARF / SYNTAXIN 1A / シンタキシン / シンコリン / 開口分泌 / ムチン / 分泌顆粒 |
Research Abstract |
In salivary gland acinar cells, the secretory function is rcgulated by two main signaling pathways via muscarinic and beta-adrenergic receptors.Stimulation of muscarinic receptors causes the increase in intracellular calcium ions (Ca^<2+>). However, the mechanism with Ca^<2+>-dependent secretory pathway has not well elucidated. We here studied with the mechanism of exocytosis via Ca^<2+> signaling pathway. During this study, we first demonstrated that the increase in intracellular Ca^<2+> induced by muscarinic receptor stimulation activated nitric oxide synthase. Subsequently, nitric oxide generated stimulated soluble guanylyl cyclase and induced cyclic GMP formation in salivary gland acinar cells. We next found that Arfi, a small GTP-binding protein, existed in rat parotid acinar cells. Furthermore, we demonstrated that the Arf1 translocated to secretory granules in the presence of GTP gammaS. Rat sublingual gland acinar cells are an useful model for the study with Ca^<2+>-dependent exocytosis, since Ca^<2+>-mobilizing receptor activation induces mucin exocytosis. We found that high concentration of syntaxin1A in the membrane fraction of sublingual acinar cells by immuno blotting. The expression of mRNA of syntaxin1A was detected in rat salivary glands such as sublingual and submandibular glands. However, we failed to detectthe binding proteins to syntaxinlA such as VAMP-2 and SNAP-25. Further studies with the relationship between syntaxin1A and Ca^<2+>-nitric oxide-cyclic GMP signaling and identification of syntaxin 1A binding proteins are necessary.
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