1998 Fiscal Year Final Research Report Summary
The role of Ca^<2+>-activated K^+ channels of tracheal smooth musde on anti-asthmatic agents
| Project/Area Number |
09670606
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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 |
Respiratory organ internal medicine
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| Research Institution | Nagoya University |
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Principal Investigator |
TAKAGI Kenzo School of Medicine, Nagoya University Professor, 医学部, 教授 (50093050)
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| Co-Investigator(Kenkyū-buntansha) |
KUME Hiroaki School of Medicine, Nagoya University Professor Associate, 医学部, 助手 (50303631)
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| Project Period (FY) |
1997 – 1998
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| Keywords | bronchial asthina / tracheal smooth muscle / Ca^<2+>-activated K^+ channels / beta-stimulant / forskolin / NKH477 / atrial natriuretic peptide / uroguanylin |
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| Research Abstract |
In order to clarify the role of Ca^<2+>-activated K^+ channels in anti-asthmatic agents, effects of a new water-soluble forskolin derivative (NKH477), beta-agonists, atrial natriuuretic peptide (ANP) and uroguanylin on tracheal smooth muscle isolated from guinea-pigs or humans were investigated. We have demonstrated that the bronchorelaxant action of NKH477 may result, at least in part, from activation of Ca^<2+>-activated K^+ channels, which may cause a hyperpolarization of smooth muscle cell membranes as well as beta-agonists. In addition, we showed that continuous and repeated exposure to. beta-agonists leads to beta-adrenergic desensitization, and that activation of Oa^<2+>-activated K^+ channels by Gs prevents this ddesensitization in guinea-pigs and human trachealis. On the other hand, intravenous pretreatment of uroguanylin significantly inhibited ovalbumin-induced bronchoconstriction and microvascular leakage in a dose-dependent manner. These findings are the first to show that uroguanylin has potent bronchodilatory effect. We further demonstrated that augmentation of the activity of Ca^<2+>-activated K^+ channels plays a functionally important role in the cGMP-induced relaxation in human airway smooth muscle, and that ANP may have modest potency as a bronchodilator. Our results suggest the possibility that agents via Ca^<2+>-activated K^+ channels are useful for the treatment of asthmatic patients.
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Research Products
(18 results)
