Serotonin inhibits Na+/H+ exchange activity via 5-HT4 receptors and activation of PKCα in human intestinal epithelial cells

Abstract

Background & Aims:: Increased serotonin levels have been implicated in the pathophysiology of diarrhea associated with celiac and inflammatory diseases. However, the effects of serotonin on Na+/H+ exchange (NHE) activity in the human intestine have not been investigated fully. The present studies examined the acute effects of 5-hydroxytryptamine (5-HT) on NHE activity using Caco-2 cells as an in vitro model. Methods:: Caco-2 cells were treated with 5-HT (.1 μmol/L, 1 h) and NHE activity was measured as ethyl-isopropyl-amiloride (EIPA)-sensitive 22Na uptake. The effect of 5-HT receptor-specific agonists and antagonists was examined. The role of signaling intermediates in 5-HT-mediated effects on NHE activity was elucidated using pharmacologic inhibitors and immunoblotting. Results:: NHE activity was inhibited significantly (∼50%-75%, P