Regulation of smooth muscle contraction through remodeling of actin filaments
| Project/Area Number |
17500277
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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 |
Neurophysiology and muscle physiology
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
WATANABE Masaru Tokyo Medical University, Department of Physiology, Lecturer, 医学部, 講師 (60191798)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | smooth muscle / actin filaments / remodeling / skinned preparation / blebbistatin / phenoxazine / gelsolin / 筋フィラメント / ブレビスタチン |
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| Research Abstract |
1)Mechanism of the inhibitory effects of Phx-1 on the smooth muscle contraction To elucidate the mechanisms of relaxing effect of 2-amino-4,4 a-dihydro-4 a-7-dimethyl-3H-phenoxazine-3-one (Phx-1) on the smooth muscle preparations, we investigated effects of Phx-1 on the contraction of both intact and skinned (cell membrane peremeabilized) preparations from guinea pig tenia cecum. In intact preparations, Phx-1 concentration-dependently suppressed the contraction induced by either acetycholine(ACh) or high-K+ with the IC50 value estimated at around 100 pM. Similar inhibitory actions of Phx-1 on force were observed in intracellular Ca store depleted preparations. In the cell membrane depolarized preparations in the absence of extracellular Ca, however, Phx-1 had little effects on the caffeine-or ACh-induced contraction. In skinned preparations, Phx-1 suppressed the Ca^<2+->induced contraction at concentrations higher than 100 μM. These results suggest that Phx-1 seems to have direct inhib
… More
itory effect on the actin filaments organization, although inhibitory effect, of the Phx-1 on the Ca^<2+>-influx is much stronger.
2)Contractile filaments remodeling by blebbistatin, a potent inhibitor of myosin II We studied the effects of blebbistatin, a potent inhibitor of myosin II on the mechanical and structural properties of beta escin skinned taenia cecum. Blebbistatin inhibited both Ca^<2+> induced contraction with only little effects on the Ca^<2+> sensitivity for the force, and 30 mM Mg^<2+> induced, myosin phosphorylation independent, force development, Also, blebbistatin accelerated relaxation by Ca^<2+> removal. IC_<50> values of the blebbistatin effects presented above were nearly 25 micro M. The present results suggested that blebbistain directly interfare cross-bridge interaction. Furthermore, blebbistatin inhibited organization of actin-and myosin-filaments. Since blebbistatin did not bind to actin directly, disruption of myosin filaments seemed to modulate actin filaments organization. Less
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Report
(3 results)
Research Products
(3 results)
