| Project/Area Number |
02404024
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
General pharmacology
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| Research Institution | Kyushu University |
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Principal Investigator |
KURIYAMA Hirosi Kyushu University, Faculty of Medicine, Professor, 医学部, 教授 (40037495)
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| Co-Investigator(Kenkyū-buntansha) |
ITOH Takeo Kyushu University, Faculty of Medicine, Lecturer, 医学部, 講師 (70159888)
KITAMURA Kenji Kyushu University, Faculty of Medicine, Lecturer, 医学部, 講師 (30112345)
ITO Yushi Kyushu University, Faculty of Medicine, Assistant Professor, 医学部, 助教授 (80037506)
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| Project Period (FY) |
1990 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥22,200,000 (Direct Cost: ¥22,200,000)
Fiscal Year 1991: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 1990: ¥17,600,000 (Direct Cost: ¥17,600,000)
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| Keywords | vascular smooth muscle / histaminergic receptor current / purinergic receptor current / GTP-binding protein / patch clamp / voltage-dependent Ca current / nonselective cation channel / ヒスタミン受容体電流 / プリン受容体電流 / パッチ固定法 / 電位依存性Ca電流 / 非選択的カチオンチャネル / 薬物ー収縮連関機構 / Ca transient測定法 / 受容体活性化 / 電位依存性Caチャネル / 百日咳毒素 |
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| Research Abstract |
TO clarify the underlying mechanism of pharinaco-mechanical coupling in vascular smooth muscle, features of the receptor-operated ion channel, effects of second messengers and mechanical responses were investigated. We clarified distributions of at least two different purinergic II receptors (PII_A and PII_B) and features of both channel currents differed. The activations of PII_A and PII_B receptor produced the fast shortlasing and slow sustained inward currents, respectively. The latter was sensitive to GTP and GTPgammaS and enhanced the current amplitude. This action was blocked by GDPbetaS. ATP at low concentrations enhanced the voltage-dependent Ca channel but high concentrations of ATP inhibited this current. This inhibition was accelerated by GTP and GTPgammaS, and prevented by GDPbetaS. Histamine also modified the ionic channel through different three subtypes, i. e. the H_1 receptor activation produced the non-selective cation channel and the H_3 receptor activation inhibited the release of transmitter (mainly noradrenaline and ATP from nerve terminals and also accelerated the voltage-dependent Ca channel. Protein kinase C independent acceleration), but the H_1-induced receptor operated nonselective cation channel was accelerated. In addition, activations of the H_2 receptor by histamine accelerated the cyclic AMP synthesis. Using fura-2 and patch-clamp procedures, when voltagedependent Ca channel and Ca transient were simultaneously recorded, amplitudes of the inward current were enhanced the Ca transient in a concentration dependent manner, this channel activity was modulated by extra- and intra-cellular Na. Presumably, in vascular smooth muscle cells, Na-Ca exchange diffusion mechanism may contribute for determine the cytosolic Ca.
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