| Project/Area Number |
05454503
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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 | HIROSHIMA UNIVERSITY |
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Principal Investigator |
DOHI Toshihiro Dept.Pharmacology, Hiroshima University School of Dentistry, Professor, 歯学部, 教授 (00034182)
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| Co-Investigator(Kenkyū-buntansha) |
MORITA Katsuya Dept.Pharmacology, Hiroshima University School of Dentistry, Associate Professor, 歯学部, 講師 (10116684)
KITAYAMA Shigeo Dept.Pharmacology, Hiroshima University School of Dentistry, Assistant Professor, 歯学部, 助教授 (80177873)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1994: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1993: ¥4,700,000 (Direct Cost: ¥4,700,000)
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| Keywords | PAF / PAF receptor mRNA / Mucin / Submandibular gland / Calcium / Acetyltransferase / Cholinephosphotransferase / Acetylcholine / Submandibular gland / Mucin / PAF / Acetylcholine / Phosphatidylinositol / Acetyltransferase / Na^+,K^+-ATPase / Calcium / Cyclic ADP ribose / Dog |
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| Research Abstract |
We have suggested that the muscarinic cholinergic system in addition to the adrenergic system participate in the regulation of mucin release in dog asubmandibular gland. However the precise mechanism of exocytotic mucin release and its regulation mechanisms are not fully understood. We have previously shown that platelet-activating factor (PAF), a potent phospholipid mediator, is synthesized by muscarinic cholinergic receptor stimulation in dog salivary glands. The present study examined the regulation of PAF biosynthesis and its role in mucin release in submandibular glands.
Norepinephrine (NE) and phenyrephrine, but not isoproterenol stimulated PAF production in submandibular gland cells. Lyso-PAF : acetyl-CoA acetyltransferase was activated in the cells treated with ACh, NE,isoproterenol and 8Br-cyclic AMP.Deprivation of Ca^<2+> in the medium markedly reduced ACh-induced activation, but little affected NE-, isoproterenol- and 8Br-cyclic AMP-induced activation. Dithiothreitol-insensit
… More
ive chlinephosphotranseferase activity was also increased by these agents, and the deprivation of Ca^<2+> in the medium further increased the activation. A part of PAF formed in the guinea pig but not dog submandibular gland cells was released into the incubation medium. PAF stimulated the release of mucin from guinea pig submandibular gland slices. The effect of PAF was Ca^<2+>-dependent and antagonized by PAF receptor antagonist BN50739. By the RT-PCR method, the expression of PAF receptor mRNA was found in the guinea pig parotid gland and submandibular gland, but not in the dog parotid gland and submandibular galnd. The amount of inositol 1,4,5-trisphosphate in guinea pig subbmandibular gland slices transiently increased by PAF over the first 5-10s. Injection of total mRNA from submandibular gland in to Xenopus oocytes expressed ACh receptors which produced Cl-current by ACh but the expression of PAF receptor has not been succeded yet (under current investigation).
These results suggest that PAF syntesis salivary glands is under the control of muscarinic cholinergic and alpha-adrenergic systems via Ca^<2+>-dependent remodelling pathways and that PAF receptors are existent in guinea pig submandibular galnds, and PAF,formed by the stimulation of cells with ACh, is partially released to the extracellular space and stimulates secretion of mucin via PAF receptor-PI turn over pathway. Less
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