| Project/Area Number |
10670083
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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 |
General pharmacology
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
AYAJIKI Kazuhide Shiga University of Medical Science, Phamacology, Associate Professor, 医学部, 助教授 (10167968)
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| Co-Investigator(Kenkyū-buntansha) |
OKAMURA Tomio Shiga University of Medical Science, Phamacology, Professor, 医学部, 教授 (70152337)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1998: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | coronary of linguial artery / endothelium / nitric oxide (NO) / endotherium-derived hyperpolarization factor (EDHF) / metabolite(s) from arachidonic acid / corpus cavernosum / nitroxidergic nerve / biocascade system / Ca^<2+>感受性K^+チャネル / チトクロームP450 / アラキドン酸 / サル舌動脈 |
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| Research Abstract |
Substances associated with endothelium-dependent or neurogenic relaxations were examined in isolated arteries and corpus cavernosum. Endothelium-derived relaxing substance other than nitric oxide (NO) and prostacyclin, and nerve-derived NO were tried to be measured by a biocascade system.
(1) In isolated monkey coronary arteries, vasopressin-induced relaxation is mediated by NO released from the endothelium via stimulation of VィイD21ィエD2 receptors.
(2) In isolated monkey lingual arteries, acelycholine (ACh)-induced, endothelium-dependent relaxation was partially inhibited by L-NA, a NO synthase inhibitor. The remaining relaxation was abolished by CィイD12+ィエD1-dependent KィイD1+ィエD1 channel blockers or cytochrome P450 (CYP) 3A-inhibitors. The biocascade system failed to detect the relaxant substance, possibly endothelium-dependent derived hyperpolarizing factor (EDHF), indicating that the substance may be unstable. Products of arachidonic acid incubated with human liver microsome containing C
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YP3A relaxed the artery, the relaxation was abolished by the KィイD1+ィエD1 channel blockers. Products co-incubated with CYP3A-inhibitors did not relax the artery. These findings suggest that the relaxation by ACh in this artery is mediated by NO and KィイD1+ィエD1-channel opening substance(s) from arachidonic acid produced by CYP3A in the endothelium.
(3) Histological studies with isolated canine corpus cavernosum demonstrated that saponin induced degenerative changes in the endothelial cells selectivity. ACh relaxed the intact, but not the saponin-treated, cavernos strips, the relaxation was partially inhibited by L-NA and the remaining relaxation was abolished by high concentration of KィイD1+ィエD1. On the other hand, neurogenic relaxation sensitive to L-NA was not affected by saponin. The nerve-derived NO was not detected by the biocascade system. These findings suggest that ACh acts on the endothelium and liberates NO and KィイD1+ィエD1-channel opening substance which relax the smooth muscle of the cavernosum. Nitroxidergic nerve function appears to be unaffected by the damage of endothelial cells. Less
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