5‐Hydroxytryptamine inhibits Na absorption and stimulates C1 secretion across canine tracheal epithelial sheets

Abstract

5-Hydroxytryptamine (5-HT) can be released from mast cells and platelets through an IgE-dependent mechanism and may play a role in the pathogenesis of allergic bronchoconstriction. However, the effect of 5-HT on ion transport by airway epithelium remains uncertain. To determine whether 5-HT alters electrical and ion transport properties of Cl-secreting epithelia and, if so, what subtype of 5-HT receptors is involved, we studied canine tracheal epithelium under short-circuit conditions in vitro. Canine tracheal mucosa was mounted in Lucite half-chambers and the responses of short-circuit current (lsc), transepithelial potential difference (PD) and tissue conductance (G) were measured. In addition, ion fluxes were directly measured using 22Na and 36Cl. Mucosal addition of 5-HT caused a rapid increase in lsc, which was accompanied by the increases in PD and G, whereas submucosal 5-HT had no effect. In the presence of amiloride, 5-HT and its receptor agonists dose-dependently increased lsc, with the rank order of potency being 5-HT > alpha-methyl-5-HT > 2-methyl-5HT > 5-carboxamidotryptamine. The effect of 5-HT was inhibited by ketanserin and spiperone but not by ondansetron. 5-HT increased Cl flux from the submucosa to the mucosa with a slight inhibition of Na flux to the opposite direction. 5-HT inhibits airway epithelial Na absorption and stimulates Cl secretion. The latter action predominates the former and is mediated by 5-HT2 receptors. These effects may result in the increase in water movement toward the airway lumen.