| Project/Area Number |
17390053
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General anatomy (including Histology/Embryology)
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| Research Institution | Iwate Medical University |
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Principal Investigator |
SATOH Yoh-ichi Iwate Medical University, Anatomy, Professor (40118253)
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| Co-Investigator(Kenkyū-buntansha) |
SAWAI Takashi Iwate Medical University, Pathology, Pathology Professor (00125577)
NAKAI Kenji Iwate Medical University, Clinical laboratory, Ass. Professor (90146035)
SAINO Tomoyuki Iwate Medical University, Anatomy, Ass. Professor (40305991)
AKUTSU Hitomi Iwate Medical University, Anatomy, Postdoctoral Fellow (30398482)
似鳥 徹 岩手医科大学, 医学部, 講師 (90128934)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥14,010,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥810,000)
Fiscal Year 2007: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2006: ¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 2005: ¥4,900,000 (Direct Cost: ¥4,900,000)
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| Keywords | Intracellular Calcium Ion / Vascular smooth muscle / Laser Scanning Confocal Microscopy / Digital imaging Analysis / Living Cell / Tissue Specimens / Protease Activated Receptors |
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| Research Abstract |
Protease-activated receptors (PARs) mediate cellular responses to various proteases in numerous cell types, including smooth muscles and the endothelium of blood vessels. PARs may also play important roles in microcirculation in tissue/organs. The issue of whether the stimulation of PARs induces responses in smooth muscle cells of arterioles was examined; with special reference to intracellular Ca^<2+>([Ca^(2+)]i) dynamics and nitric oxide (NO) production during PARs stimulation, since [Ca^(2+) ]i and NO are both key factors in the maintenance of strain in blood vessels. These were measured by real-time confocal microscopy. Arterioles were taken obtained from the brain and testis of rats. In smooth muscle cells of small cerebral arterioles (< 50 μm in diameter), thrombin and PAR1-activating peptide (AP) induced an increase in [Ca^<2+>]i and contraction. The response to PAR1 activation was caused by Ca^<2+>mobilization from intracellular Ca^<2+>stores. Trypsin and PAR2-AP induced a decrease in [Ca^<2+>] i in the cells, and this effect can be mediated by endothelium-derived NO and/or by promoting. Ca^<2+> sequestration mechanism. PAR3- and 4-AP had no effect. In contrast to small cerebral arterioles, [Ca^<2+>], dynamics in smooth muscle cells of large (<100 μ in diameter) cerebral or testicular arterioles remained unchanged during PARs activation. In accordance with [Ca^<2+>], imaging results, immunohistochemical results showed thrombin receptor and PAR2 in smooth muscles and endothelium of small cerebral arterioles, but not in larger those. The immunoreactivity of PARs in testicular arterioles was faint. This is the first study to demonstrate the effects of PARs activation on the [Ca^<2+>]I dynamics of smooth muscles and the contraction/relaxation of cerebral arterioles, implicating the significant role of proteases in the regional tissue circulation of the brain.
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