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Am J Physiol Gastrointest Liver Physiol 275: G433-G448, 1998;
0193-1857/98 $5.00
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Vol. 275, Issue 3, G433-G448, September 1998

Guinea pig 5-HT transporter: cloning, expression, distribution, and function in intestinal sensory reception

Jing-Xian Chen, Hui Pan, Taube P. Rothman, Paul R. Wade, and Michael D. Gershon

Department of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York 10032

Studies of the guinea pig small intestine have suggested that serotonin (5-HT) may be a mucosal transmitter that stimulates sensory nerves and initiates peristaltic and secretory reflexes. We tested the hypothesis that guinea pig villus epithelial cells are able to inactivate 5-HT because they express the same 5-HT transporter as serotonergic neurons. A full-length cDNA, encoding a 630-amino acid protein (89.2% and 90% identical, respectively, to the rat and human 5-HT transporters) was cloned from the guinea pig intestinal mucosa. Evidence demonstrating that this cDNA encodes the guinea pig 5-HT transporter included 1) hybridization with a single species of mRNA (~3.7 kb) in Northern blots of the guinea pig brain stem and mucosa and 2) uptake of [3H]5-HT by transfected HeLa cells via a saturable, high-affinity (Michaelis constant 618 nM, maximum velocity 2.4 × 10-17 mol · cell-1 · min-1), Na+-dependent mechanism that was inhibited by chlorimipramine > imipramine > fluoxetine > desipramine > zimelidine. Expression of the 5-HT transporter in guinea pig raphe and enteric neurons and the epithelium of the entire crypt-villus axis was demonstrated by in situ hybridization and immunocytochemistry. Inhibition of mucosal 5-HT uptake potentiates responses of submucosal neurons to mucosal stimulation. The epithelial reuptake of 5-HT thus appears to be responsible for terminating mucosal actions of 5-HT.

serotonin; serotonin-selective reuptake inhibitors; fluoxetine; enteric nervous system; peristaltic reflex; enterochromaffin cells


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