| Project/Area Number |
04670455
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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 |
Respiratory organ internal medicine
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| Research Institution | Tohoku University |
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Principal Investigator |
ICHINOSE Masakazu Tohoku University School of Medicine, Assistant, 医学部・附属病院, 助手 (80223105)
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| Project Period (FY) |
1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1992: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | bronchial asthma / chronic bronchitis / axon reflex / airway inflammation / neuropeptide / substance P / Allergic inflammation / neurogenic inflammation / 好酸球 / 慢性炎症 / タヒキニン |
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| Research Abstract |
(1) Evidence of axon reflex mechanisms in human airways
In a double-blind, placebo-controlled, crossover trial, ten subjects with asthma were given a tachykinin receptor antaqonist (FK 224) or placebo by inhalation 20 min before challenge of bradykinin given with 5 min intervals. Bradykinin caused dose-dependent bronchoconstriction in all subjects. FK 224 significantly opposed the bronchoconstrictor effect ; the geometric mean of the cumulative concentration required to elicit a 35% fall in specific airway conductance was 5.3 mug/ml afater placebo and 40 mug/ml after FK 224. Inhalation of bradykinin caused coughing in three subjects, which was inhibited by FK 224 in all three. These results, which was inhibited by FK 224 in all three. These results suggest that tachykinin release from airway sensory nerves is involved in response to bradykinin in the patients with asthma.
(II) Modulation of neurogenic inflammation
We examined the effect of NPY and ibudilast on neurogenic microvascular leakage in guinea-pig airways by measuring extravasation. Both compounds significantly inhibited bilateral vagal nerve stimulation-induced responses, but the exogenous SP-mediated responses were not influenced by these agents, suggesting that these drugs inhibit neurogenic leakage by prejunctional inhibition of neuropeptide release from airway sensory nerve terminals. Furthermore, we have shown that the inhibitory effect of ibudilast was via ATP-sensitive K channels but the effect of NPY was not.
(III) Chronic airway inflammation model
We examined the excitatory nerve function after repeated allergen inhalation challenge in sensitized guinea-pigs. 4 wks allergen inhalation significantly enhanced both cholinergic and noncholinergic bronchoconstriction without affecting the response to exogenous ACh and NKA.We concluded that the enhancement of these nerve function was caused by enhancing neurotransmitter production and/or release.
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