Abstract
Recent clinical and experimental studies have demonstrated that 14-membered macrolides suppress fluid secretion from respiratory tract mucosa. The cellular mechanisms of acetylcholine (ACh) -induced electrolyte secretion in acinar cells isolated from guinea pig nasal glands were investigated using a microfluorimetric imaging method and patch-clamp wholecell recording. The ACh-induced increase in the intracelluar Ca2+ concentration as measured by the fura-2 method was little affected by three types of macrolides, josamycin (JM), erythromycin (EM), and roxithromycin (RXM). The ACh-evoked ionic currents were not inhibited by a 16-membered macrolide, JM, whereas both 14-membered macrolides, EM and RXM, significantly inhibited membrane conductance, especially inward Cl- currents. The order of inhibition was RXM > EM >> JM. Thus, 14-membered macrolides showed a direct inhibition of the Cl- conductance activated by ACh.
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