The gastrointestinal tract is an important source of the endogenous amine, serotonin, mainly stored in the mucosal enterochromaffin cells and in the enteric nervous system (1).
5-HT1 is continuously released from the enterochromaffin cells in the intestinal mucosa into the portal circulation and the gut lumen in response to a variety of luminal stimuli such as change in pH or osmolarity and mechanical and chemical stimuli (2). 5-HT is an important neurotransmitter and intercellular messenger to modulate gastrointestinal functions (3). 5-HT has been shown to alter gastrointestinal motility (4), alter gastric acid secretion, and enhance intestinal secretions (1, 5). Most of the previous studies regarding the effects of serotonin on ion transport were mainly based on the electrophysiological data including short circuit current measurements and unidirectional fluxes. These studies showed that 5-HT stimulated electrogenic Cl Ϫ secretion and inhibited Na ϩ and Cl Ϫ absorption in the rat colon (6), jejunum (7), ileum (8), and guinea pig ileum (9). 5-HT has also been shown to inhibit the NaClabsorptive process in the rabbit ileum and gall bladder (10) but has no effect in rabbit and guinea pig colon (10, 11). Moreover, Sundaram et al. (12) have demonstrated that 5-HT inhibits Cl Ϫ /HCO 3 Ϫ exchange activity in villus cells and stimulates HCO 3 Ϫ secretion in crypt cells of the rabbit ileum. In contrast, 5-HT appears to have no significant effect on coupled NaCl absorption in the human jejunum (13).5-HT exerts its effects by binding to 5-HT receptors, which are distributed on the neuronal, muscular, and epithelial structures (14). Based on pharmacological studies and molecular cloning (15), the existence of at least seven 5-HT receptors (5-HT1-7) subdivided into 14 subtypes has been discovered. With the exception of 5-HT5 and 5-HT6, 5-HT1 A , 5-HT1 P , 5-HT2, 5-HT3, and 5-HT4 have been reported to be expressed in the gut (16). 5-HT1, 5-HT2, and 5-HT4 receptors are coupled via guanine nucleotide binding (G) proteins to their effectors, whereas 5-HT3 receptor is a ligand-gated ion channel permeable to anions and cations (17).