Cholinomimetic action of macrolide antibiotics on airway gland electrolyte secretion

Toshiya Irokawa, Tsukasa Sasaki, Sanae Shimura, Kan Sasamori, Takako Oshiro, Masayuki Nara, Tsutomu Tamada, Kunio Shirato

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

We investigated the acute effects of erythromycin (EM) and its derivatives on ionic currents in airway glands from feline tracheae. Therapeutic concentrations of EM or clarithromycin (CAM) attenuated the whole cell currents evoked by ACh in a competitive manner. The maximally stimulated inward Cl- currents were reduced to 54 and 83% and the outward K+ currents to 55 and 84% of control values by EM and CAM, respectively, whereas the responses induced by phenylephrine, norepinephrine, caffeine, or ionomycin were unaffected by EM, CAM, or EM523, 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 Cl- secretion at pharmacological doses of the agents, which may exhibit a pronounced effectiveness on hypertrophied and/or cholinergically sensitized submucosal glands in pathological airways.

Original languageEnglish
Pages (from-to)L951-L957
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume276
Issue number6 20-6
DOIs
Publication statusPublished - 1999 Jun

Keywords

  • Chloride secretion
  • Erythromycin
  • Partial agonist
  • Patch clamp
  • Submucosal gland

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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