| Project/Area Number |
61440029
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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 Faculty of Medicine, Kyushu University, Professor, 医学部, 教授 (40037495)
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| Co-Investigator(Kenkyū-buntansha) |
ITOH Takeo Faculty of Medicine, Kyushu University, Assistant, 医学部, 助手 (70159888)
KITAMURA Kenji Faculty of Medicine, Kyushu University, Assistant Professor, 医学部, 講師 (30112345)
SUZUKI Hikaru Faculty of Medicine, Kyushu University, Assistant Professor, 医学部, 講師 (80037548)
ITO Yushi Faculty of Medicine, Kyushu University, Associate professor, 医学部, 助教授 (80037506)
平田 雅人 九州大学, 歯学部, 講師 (60136471)
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| Project Period (FY) |
1986 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥28,800,000 (Direct Cost: ¥28,800,000)
Fiscal Year 1987: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1986: ¥25,800,000 (Direct Cost: ¥25,800,000)
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| Keywords | Prostaglandin E_2, F_<2<alpha>> / thromboxane A_2 / leucotrien D_4 / vascular smooth muscles / intestinal smooth muscle / oviduct smooth muscle tissues / secondary messengers / 大動脈 / プロスタグランジン / トロンボキサン【A_2】 / ロイコトリエン / セコンドメッセンジャー / 細胞内Ca |
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| Research Abstract |
Following discovery of the arachidonic cascade, many physiologically active substances were elucidated as metabolic products of arachidonic acid through activations of cycloxygenase and lopoxygenase. However, actions of these physiologically active substances (autacoids) on smooth muscle tissues are not yet understood in detail. The present researches were intended to clarify the nature of primary prostanoids (prostaglandin E_2 and prostaglandin F_<2<alpha>>;PGE_2 and PGF_<<alpha>>), thromboxane A_2 (TXA_2; the present experiments, mainly used an analogue og TXA_2 STA_2), prostaglandin I_2(PGI_2; prostacyclin) and leucotrien D_4, using biophysical and biochemical procedures. In vascular smooth muscles (coronary and basilar arteries), TXA_2 (STA_2) did not depolarized the membrane but enhanced the contraction ampitude and in the absence of Ca, STA_2 still producedthe contraction with a reduction in the amplitude. Ca antagonist nifedipien slightly inhibited the STA_2-induced contraction.
… More
Thus, STA_2 enhances the voltage dependent and receptor opearated Ca channel and increases the amount of free Ca in the cell. Furthermore, STA_2 releases Ca from the sarcoplasmic reticulum as estimated from the contraction evoked in the absence of Ca through hydrolysis of phosphatidyl inositol 4,5-bisphophate. Much the same responses were observed by application of LTD_4 but the responses induced by LTD_4 were weaker than those observed by application of STA_2. STA_2 also releases endothelium deived relaxing factor by stimulation of endothelium. PGI_2 was released from the endothelium and smooth muscle cells by stumulation of ACh or high K. The former released PGI_2 to the greater extent than the latter. PGI_2 increased cyclic AMP and reduced the free Ca in the cytosol. PGI_2 released from the endothelium may have little action on the relaxxation of smooth muscles but that released from smooth muscles may directly reduced the precontracted tissues. Primary prostanoids act on the intestinal smooth muscles. In vascular tissues, indomethacine enhanced the excitatory junction potential (e.j.p.) but in the intesine it inhibited the amplitude of e.j.p.. applied PGE_2 reduced the e.j.p. in vascular smooth muscles but enahced in the intestine. Furthermore, in the intesitine, PGE_2 enhanced the mechanical response without any change in the membrane potential. PGE_2 and PGF_<2<alpha>> also specifically act on human oviduct and regulated the oavl transportation as regulator of spontaneously generated action potential and contraction. Less
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