| Project/Area Number |
11672191
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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 | TOHO University |
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Principal Investigator |
SATOH Mitsutoshi Pharmaceutical Sciences, Department of Toxicology & Pharmacology, TOHO University, Lecturer, 薬学部, 講師 (60231346)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Receptors / Smooth muscle / Intracellular signal transduction / Intracellular Ca^<2+> changes / Ca^<2+> channel / Ca^<2+> store / Contraction mechanism / Neuro-transmission |
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| Research Abstract |
In this study pharmacological profiles of intracellular Ca^<2+> changes and receptor-mediated regulation of contraction in smooth muscle were studied. In ileal longitudinal smooth muscle from guinea pig. Two-dimensional images of Ca^<2+> oscillations were obtained at 33-msec intervals with a Ca^<2+>-sensitive fluorescence probe, fluo-3 using the intensified CCD camera. Nicardipine (10^<-7> M) significantly decreased the maximum level of fluorescence intensity of the Ca^<2+> oscillations, inhibited the frequency of the oscillations, and tended to decrease the basal level of fluorescence intensity. However, tetrodotoxin (3 X 10^<-7> M) did not affect these oscillations. Phorbol 12, 13-dibutyrate (10^<-7> M) significantly increased the maximum level of fluorescence intensity and the frequency of Ca^<2+> oscillations, and changed them to steady and chronometric Ca^<2+> oscillations. Cyclopiazonic acid (3 X 10^<-5> M) also significantly increased the frequency of Ca^<2+> oscillations. Acetylcholine (10^<-8> M) increased the basal and maximum level of fluorescence intensity and the frequency of Ca^<2+> oscillations, and accelerated their on set. The increase of basal level of fluorescence intensity was then decreased by cyclopiazonic acid treatment. These results suggest that the augmentation of Ca^<2+> oscillations is mainly due to the activation of L-type Ca^<2+> channels, which is modulated by protein kinase C, and that the emptying of intracellular Ca^<2+> stores may activate the Ca^<2+> oscillations mediated through the increase of Ca^<2+> influx in ileal smooth muscle of guinea pig.
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