1988 Fiscal Year Final Research Report Summary
Intractable asthma -Pathogenesis and treatment-
| Project/Area Number |
62480204
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Nagoya University |
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Principal Investigator |
SATAKE Tatsuo Nagoya University School of Medicine. Professor, 医学部, 教授 (60023743)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAKI Kenichi Nagoya University School of Medicine. Assistant, 医学部, 助手 (20182420)
SUZUKI Ryuziro Nagoya University School of Medicine. Assistant, 医学部, 助手 (60179273)
TAKAGI Kenzo Nagoya University School of Medicine. Lecture, 医学部, 講師 (50093050)
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| Project Period (FY) |
1987 – 1988
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| Keywords | Intractable Asthma / -adrenergic Blockade / Phospholipase A_2 / ,-adrenoceptor / New Xanthine Derivatives / 1 Methy-3propylxanthine / Colforcin / 1メチルー3プロピルーキサンチン / コルフォルシン / 抗コリン薬 |
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| Research Abstract |
1. Pathogenesis and pathophysiology of bronchial asthma (1)After allergen challenge, some asthmatic patients showed dual asthmatic response. An increase of of serum LTB<@D24@>D2 preceded a decrease of FEV 1.0 in late asthmatic response. (2)Phospholipase (PLase) activity in lung membranes, LTB<@D24@>D2 and cellular changes of lung lavages from ovalbumin(OA)-challenged guinea pigs were assessed before and at regular intervals for as long as 24h after OA challenge. Just after inhalation, PLase activity was increased and an increase of LTB<@D24@>D2 was also observed. On the other hand, the number of neutrophils was increased at 3h, while the number of eosinophils was increased at 6h. (3)The number of -adrenoceptor in lung membranes of OA-challenged guinea pigs was decreased by more than 30% compared with that of control subjects, while the number of -adrenoceptor was increased by 37%. These changes were revealed to be linked with altered phospholipid composition induced by PLase A<@D22@>D1
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activaltion.
2. Development and clinical applications of new bronchodilating agents We have already reported a drug which shows relaxant effect on brochial smooth muscle via elevating cyclic GMP. (1)Anti-cholinergic drugs:An abnormality of cholinergic system is closely related to the pathogenesis of bronchial asthma. So, anti-cholinergic drugs were expected to show a favarabel effect. An anti-cholinergic drug could decrease a number of muscarinic acetylcholine receptors in the lung of experimental, animals. Furthermore, adverse effect of this drug scaresely occurred. (2)A new xanthine derivatives:We demonstrated that 1-methyl-3propylxanthine has a great potency of bronchodilation. This agent also has a strong action of inhibitory high affinity cyclic AMP phoshodiesterase. (3)Colforcin:Colforcin has a potent relaxant effect on tracheal smooth muscle via direct adenylate cyclase activation. This drug has also cardiovascular effect. So, further investigation is needed before clinical application. Less
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