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Journal of Neuroscience, Vol 16, 2352-2364, Copyright © 1996 by Society for Neuroscience
Localization and function of a 5-HT transporter in crypt epithelia of the gastrointestinal tract
PR Wade, J Chen, B Jaffe, IS Kassem, RD Blakely and MD Gershon
Department of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, 10032, USA.
The peristaltic reflex can be evoked in the absence of input from the CNS
because the responsible neural pathways are intrinsic to the intestine.
Mucosal enterochromaffin cells have been postulated to be pressure
transducers, which activate the intrinsic sensory neurons that initiate the
reflex by secreting 5-HT. All of the criteria necessary to establish 5-HT
as this transmitter have been fulfilled previously, except that no mucosal
mechanism for 5-HT inactivation was known. In the current investigation,
desensitization of 5-HT receptors was demonstrated to inhibit the
peristaltic reflex in the guinea pig large intestine in vitro. At low
concentration (1.0 nM), the 5-HT uptake inhibitor fluoxetine potentiated
the reflex, but higher concentrations blocked it, suggesting that the
peristaltic reflex depends on the 5-HT transporter-mediated inactivation of
5-HT. Specific (Na+ -dependent, fluoxetine-sensitive) uptake of 3H-5-HT by
intestinal crypt epithelial cells was found by radioautography. mRNA
encoding the neuronal 5-HT transporter was demonstrated in the intestinal
mucosa by Northern analysis and located in crypt epithelial cells as well
as in myenteric neurons by in situ hybridization. cDNA encoding the 5-HT
transporter was cloned from the mucosa and completely sequenced. 5-HT
transporter immunoreactivity was detected in crypt epithelial cells and
enteric neurons. Mucosal epithelial cells thus express a plasmalemmal 5-HT
transporter identical to that of serotonergic neurons. This molecule seems
to play a critical role in the peristaltic reflex.
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