Inhibition of acetylcholine-evoked Cl- currents by 14-membered macrolide antibiotics in isolated acinar cells of the guinea pig nasal gland.
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.
Ikeda
K
K
Department of Otorhinolaryngology, Tohoku University School of Medicine, Sendai, Japan.
Wu
D
D
Takasaka
T
T
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D018118:Chloride Channels / Q000187:drug effects*; D004553:Electric Conductivity; D006168:Guinea Pigs; D007091:Image Processing, Computer-Assisted; D017136:Ion Transport / Q000187:drug effects; D018942:Macrolides / Q000494:pharmacology*; D008564:Membrane Potentials; D008856:Microscopy, Fluorescence; D009297:Nasal Mucosa / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques
D000900:Anti-Bacterial Agents; D018118:Chloride Channels; D018942:Macrolides; D000109:Acetylcholine; D002118:Calcium