| Project/Area Number |
07672392
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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 |
Biological pharmacy
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| Research Institution | Hoshi University |
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Principal Investigator |
MISAWA Miwa Hoshi University School of Pharmacy, professor, 薬学部, 教授 (20061294)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1996: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1995: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | bronchial asthma / airway hyperresponsiveness / muscarinic receptors / G protein / Ca^<2+> channel / neurokinins / beta-receptors / 気道過敏性 / 気管支平滑筋 / sensory neuropeptide / ACh受容体 / neutral endopeptidase / Ca availability |
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| Research Abstract |
The mechanisms of airway hyperresponsiveness (AHR) which lays behind bronchial asthma were investigated with rat allergy-induced AHR model developed by us. The following results were obtained.
1. Affinity of high affinity agonist binding sites of muscarinic receptor on bronchus was remarkably enhanced in AHR rats. The high affinity seemed to be linked to an increase in G protein level.
2. The bronchial constriction induced by cumulative administration of Ca^<2+> when preincubated with ACh under Ca^<2+>-free condition was significantly greater in AHR bronchus than in normal one. This suggests that availability of Ca^<2+> that liberates from sarcoplasmic reticulum and/or influxes into cells through receptor-operated Ca^<2+> channel is augmented in AHR.
3. The neutral endopeptidase (NEP) activity of AHR bronchus was decreased, and NEP inhibitors themselves enhanced the ACh-induced bronchial constriction. It is therefore suggested that neurokinins accumulation in bronchial tissues evokes an incrased ACh release from cholinergic nerve endings through NK_2 receptors which leadsto AHR.
4. Taking consideration of the results on receptor binding assays, the function and number of beta-receptors in bronchial tissues are unaltered in AHR,which denies the involvement of down-regulation of beta-receptors in the development of AHR.
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