LOCALIZATION AND FUNCTION OF A 5-HT TRANSPORTER IN CRYPT EPITHELIA OFTHE GASTROINTESTINAL-TRACT

The peristaltic reflex can be evoked in the absence of input from the CNS because the responsible neural pathways are intrinsic to the intes tine. Mucosal enterochromaffin cells have been postulated to be pressu re transducers, which activate the intrinsic sensory neurons that init iate the reflex by secreting 5-HT. All of the criteria necessary to es tablish 5-HT as this transmitter have been fulfilled previously, excep t that no mucosal mechanism for 5-HT inactivation was known. In the cu rrent investigation, desensitization of 5-HT receptors was demonstrate d to inhibit the peristaltic reflex in the guinea pig large intestine in vitro. At low concentration (1.0 nM), the 5-HT uptake inhibitor flu oxetine potentiated the reflex, but higher concentrations blocked it, suggesting that the peristaltic refer depends on the 5-HT transporter- mediated inactivation of 5-HT. Specific (Na+-dependent, fluoxetine-sen sitive) uptake of H-3- 5-HT by intestinal crypt epithelial cells was f ound by radioautography. mRNA encoding the neuronal 5-HT transporter w as demonstrated in the intestinal mucosa by Northern analysis and loca ted in crypt epithelial cells as well as in myenteric neurons by in si tu hybridization. cDNA encoding the 5-HT transporter was cloned from t he mucosa and completely sequenced. 5-HT transporter immunoreactivity was detected in crypt epithelial cells and enteric neurons. Mucosal ep ithelial cells thus express a plasmalemmal 5-HT transporter identical to that of serotonergic neurons. This molecule seems to play a critica l role in the peristaltic reflex.