J. Tamaoki et al., 5-HYDROXYTRYPTAMINE INHIBITS NA ABSORPTION AND STIMULATES CL SECRETION ACROSS CANINE TRACHEAL EPITHELIAL SHEETS, Clinical and experimental allergy, 27(8), 1997, pp. 972-977
Background 5-Hydrozytryptamine (5-HT) can be released from mast cells
and platelets through an IgE-dependent mechanism and may play a role i
n the pathogenesis of allergic bronchoconstriction. However, the effec
t of 5-HT on ion transport by airway epithelium remains uncertain. Obj
ective To determine whether 5-HT alters electrical and ion transport p
roperties of Cl-secreting epithelia and, if so, what subtype of 5-HT r
eceptors is involved, we studied canine tracheal epithelium under shor
t-circuit conditions in vitro. Methods Canine tracheal mucosa was moun
ted in Lucite half-chambers and the responses of short-circuit current
(Isc), transepithelial potential difference (PD) and tissue conductan
ce (G) were measured. In addition, ion fluxes were directly measured u
sing Na-22 and Cl-36. Results Mucosal addition of 5-HT caused a rapid
increase in Isc, which was accompanied by the increases in PD and G, w
hereas submucosal 5-HT had no effect. In the presence of amiloride, 5-
HT and its receptor agonists dose-dependently increased Isc, 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 ketanseri
n and spiperone but not by ondansetron. 5-HT increased Cl flux from th
e submucosa to the mucosa with a slight inhibition of Na flux to the o
pposite direction. Conclusion 5-HT inhibits airway epithelial Na absor
ption 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.