| Project/Area Number |
11672160
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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 |
Biological pharmacy
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| Research Institution | Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, The University of Tokyo |
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Principal Investigator |
URUSHIDANI Tetsuro Lab.of Pharmacol.& Toxicol., Grad.Sch.of Pharm.Sci., The Univ.Tokyo, Assistant Professor., 大学院・薬学系研究科, 助教授 (40262159)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAO Taku Lab.of Pharmacol.& Toxicol., Grad.Sch.of Pharm.Sci., The Univ.Tokyo, Professor., 大学院・薬学系研究科, 教授 (30217971)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | gastric secretion / gastric gland / β-escin / digitonin / phosphatidylinositol transfer protein / rabbit / βエシン / ジギトニン / phosphatidylinositol transfer protein / プロテインキナーゼ |
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| Research Abstract |
The aim of the present study was to analyze the signal transduction in the gastric parietal cell using two permeabilized cell models.
(1) Using β-escin permeabilized gastric gland model, we examined the effects of inhibitory peptides for various kinases and functional domains of several small GTP-binding proteins in order to identify the proteins downstream of cAMP.We found a possible involvement of a myosin light chain kinase-like enzyme was involved in the downstream of A-kinase, whereas the involvement of other kinases was minimum. Among various small GTP-binding proteins, only Arf showed significant effects. When acid secretion by β-escin permeabilized glands was inhibited by GTPγS, Arf was accumulated in the membrane fraction suggesting the possible involvement of Arf in the vesicular transport. These results were published in Am.J.Physiol.
(2) We tried to purify the essential components in the cytosol using digitonin-permeabilized glands where cytosolic factors were lost. Combination of various chromatographic technique, we identified two activating factors. Of these, the higher one was identified as phosphatidylinositol transfer protein. We also purified a inhibitory factor, whereas we have not identified it as it appeared to be a complex of several multiple components. We could suggest a novel mechanism of activation of acid secretion that stimulation elicits the release of inhibitory factor from the membrane. These results are featured in two papers one of which is now accepted in Am.J.Physiol.
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