| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Research Abstract |
1.Cough hypersensitivity caused by passive sensitization with protein fraction of Aspergillus restrictus strain A-17
We examined the sensitivity of the cough reflex to inhaled citric acid in guinea pigs that had been passively sensitized with the protein fraction of Aspergillus restrictus strain A-17. The number of coughs elicited by an aerosol of 5 % citric acid was significantly increased in the sensitized group compared to the non-sensitized group. The number of citric acid-induced coughs in sensitized guinea pigs was dose-dependently and significantly reduced to the level in non-sensitized guinea pigs when animals were pretreated with fexofenadine, a selective histamine H1 receptor antagonist, 60 min before citric acid inhalation. The bronchial responsiveness to inhaled methacholine or histamine in the sensitized group was not significantly heightened compared to the non-sensitized group. These results suggest that passive sensitization with the protein fraction of A. restrictus enh
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ances the excitability of cough receptors to tussive stimuli, and the physiologic features of this animal model are consistent with those of atopic cough.
2.Effect of VDM11, an anandamide transporter inhibitor, on capsaicin-induced cough in mice
It is unknown whether the anandamide membrane transporter plays a role in this modulation. To test this hypothesis, we investigated the effects of VDM11, an anandamide membrane transporter inhibitor, on capsaicin- and anandamide-induced cough. The effect of VDM11, an anandamide membrane transporter inhibitor, on capsaicin- and anandamide-induced cough in mice was examined. VDM11, at doses of 3-10 mg/kg subcutaneously, produced a dose-dependent antitussive effect. This antitussive effect was antagonized by pretreatment with either intraperitoneal administration (3 mg/kg) or inhalation (1mg/ml) of SR141716A, a cannabinoid receptor (CB1) antagonist. When capsazepine (0.3 mM), a selective TRPV1 receptor antagonist, was given via aerosol for 4 min before inhalation of 3 mg/ml of anandamide, the number of coughs was significantly decreased to the levels observed with 10% DMSO alone. These results suggest that anandamide, an endogenous cannabinoid ligand, may modulate cough sensitivity and that anandamide transporters play an important role in this modulation. Less
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