Mechanism of endothelin-induced asthma
| Project/Area Number |
04670462
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
呼吸器内科学
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| Research Institution | University of Tokyo |
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Principal Investigator |
OKABE Tetsuro Faculty of Medicine, Assistant Prof., 医学部(病), 助手 (80169135)
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| Co-Investigator(Kenkyū-buntansha) |
FUJISAWA Michio Health Service Center, Assistant Prof., 保健センター, 助手 (60218998)
萩原 弘一 東京大学, 医学部(病), 助手 (00240705)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1993: ¥600,000 (Direct Cost: ¥600,000)
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| Keywords | endothelin / asthma / prostaglandin / pyrogen / receptor |
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| Research Abstract |
Inhalation of aerosol of endothelin-1 induced dyspneal behavior in conscious guinea pigs pretreated with histamine or methacholine inhalation, while inhalation of endothelin-1 per se could not provoke dyspneal behavior in the animals. The dyspneal response was not affected either by nifedipine, a calcium channel blocker or by diphenhydramine, an antihistamine drug. Interestingly, the dyspneal response was potently inhibited by indomethasin, a cycolooxigenase inhibitor. In contrast, it has been shown that contraction of guinea pig tracheal strips induced by endothelin-1 was strongly inhibited by nifedipine in vitro. It has been also shown that both types of endothlein receptors (ETA and ETB) are present in lung tissues.
Injection of endothelin-1, or 4-Ala-endothelin-1 (a ETB receptor specific agonist) caused elevation of body temperature in conscious rabbits. The pyrogenic action by endothelin-1 was also inhibited by indomethacin.
Together with these observations the dyspneal response by endothelin appears to be induced by producing cyclooxigenase metabolites through selective stimuation of ETB receptor. We have clarified two novel roles of endothelin in vivo ; ie., dyspneal response and pyrogenic action, both of which are mediated by cyclooxigenase metabolites.
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Report
(3 results)
Research Products
(18 results)
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[Publications] Koshi, T., Torii, T., Arai, K., Edano, T., Hirata, M., Ohkuchi, M., and Okabe, T.: "Inhibition of endothelin (ET)-1- and ET-2-induced vasoconstriction by anti-ET-1 monoclonal antibody." Chem.Pharm.Bull.39. 326-329 (1991)
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[Publications] Arai, K., Koshi, T., Edano, T., Ohkuchi, M., Hirata, M., and Okabe, T.: "Characterization of immunoreactive endothelin in human urine." Biochem.Biophys.Res.Commun.182. 1506-1513 (1992)
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[Publications] Koshi, T., Etoh, Y., Torii, T., Wada, Y., Hirata, M., Ohkuchi, M., and Okabe, T.: "Induction of dyspnea by aerosol of endothelin-1/histamine or/methacholin in the conscious guinea pig." Chem.Pharm.Bull.40. 1064-1065 (1992)
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[Publications] Koshi, T., Edano, T., Arai, K., Suzuji, C., Ehara, Y., Hirata, M., Ohkuchi, M., and Okabe, T.: "Pyrogenic action of endothelin in conscious rabbit." Biochem.Biophys.Res.Commun.186. 1322-1326 (1992)
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[Publications] Edano, T., Arai, K., Koshi, T., Torii, T., Ohshima, T., Hirata, M., Ohkuchi, M., and Okabe, T.: "Digesion of endothlin-1 on cultured vascular smooth muscle cells." Cehm.Pharm.Bull.(in press). (1994)
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[Publications] Edano, T., Arai, K., Ohshima, T., Koshi, T., Hirata, M., Ohkuchi, M., and Okabe, T.: "Purification and characterization of endothelin-1 digestion activity from porcine kidney." Chem.Pharm.Bull.(in press). (1994)
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