Inhibition of acetylcholine-evoked Cl- currents by 14-membered macrolide antibiotics in isolated acinar cells of the guinea pig nasal gland.

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Abstract
Recent clinical and experimental studies demonstrated that 14-membered macrolides suppressed fluid secretion from respiratory tract mucosa. The cellular mechanisms of acetylcholine (ACh)-induced electrolyte secretion in the acinar cell isolated from the guinea pig nasal gland were investigated by using a microfluorimetric imaging method and a patch-clamp whole-cell recording. The ACh-induced increase in intracellular Ca2+ concentration measured by the fura-2 method was little affected by three types of macrolides, josamycin (JM), erythromycin (EM), and roxythromycin (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 currents, in a concentration-dependent manner. The ACh-induced Cl- current isolated by the ionic substitutional experiments was remarkably inhibited by EM and RXM. 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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