| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1997: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
1. We have compared the expression of CFTR (Cystic Fibrosis Transmembrane Conductance Regulator)-mRNA in tracheal epithelium in control rabbits and bronchitis model rabbits which were exposed to SO2-gas for 5-7 wk. The Northern blot analysis revealed a strong expression of CFTR-mRNA in SO_2-exposedepithelium but not in control healthy rabbits. Taken together with the results obtained in elctrophysiological and immunohistochemical studies, we concluded that the signature current identified in bronchitic epithelium was mediated by upregulated CFTR C1^- channel in bronchitic epithelium.
2. We investigated the acute effects of erythromycin (EM) and its derivatives on ionic currents in airway glands from feline tracheas. Therapeutic concentrations of EM or clarithromycin (CAM) attenuated the whole cell currents evoked by acetylcholine (ACh) in a competitive manner. The maximally stimulated inward C1^-currents were reduced to 54 and 83 96, and the outward K^+- currents to 55 and84 96 of controls by EM and CAM, respectively, whereas the responses induced by phenylephrine, norepinephrine, caffeine or ionomycin were unaffected by EM,CAM or EMS 23, a synthetic derivative of EM.K^+ channels in excised outside-out patches were not influenced by macrolides. Although therapeutic concentrations of macrolides showed no effect on the baseline currents, high concentrations of macrolides alone evoked currents mimicking the ACh-response, which were abolished completely by atropine. We concluded that macrolides act as a partial agonist on cholinergic receptors, resulting in a reduction of C1^- secretion atpharmacological doses of the agents, which may exhibit a pronounced effectiveness on hypertrophied and/or cholinergically-sensitized submucosalglands in pathological airways.
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