Side specific effect of 5-hydroxytryptamine on NaCl transport in the apical and basolateral membrane of rat tracheal epithelia

摘要

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 the airway epithelium is still controversial. The objective of this study was to determine whether 5-hydroxytryptamine (5-HT) regulates NaCl transport by different mechanisms in the apical and basolateral membrane of tracheal epithelia. We studied the rat tracheal epithelium under short-circuit conditions in vitro. Short-circuit current (I-sc) was measured in rat tracheal epithelial monolayers cultured on porous filters. 5-HT inhibited Na+ absorption [measured via Na+ short-circuit current (I-sc(Na))] in the apical membrane and stimulated Cl- secretion [measured via Cl- short-circuit current (I-sc(Cl))] in the basolateral membrane. Functional localization using selective 5-HT agonists and antagonists suggest that ICscl is stimulated by the basolateral membrane-resident 5-HT receptors, whereas I-sc(Na) is inhibited by the apical membrane-resident 5-HT2 receptors. The basolateral addition of 5-HT increases intracellular cAMP content, but its apical addition does not. The addition of BAPTA/AM blocked the decrease of I-sc(Na) which was induced by the apical addition of 5-HT, and 5-HT increased intracellular Ca concentrations. These results indicate that 5-HT differentially affects I-sc(Na) and I-sc(Cl) across rat tracheal monolayers through interactions with distinct receptors in the apical and the basolateral membrane. These effects may result in an increase of water movement towards the airway lumen.