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Localization and function of a 5-HT transporter in crypt epithelia of the gastrointestinal tract. J Neurosci 1996 Apr 01;16(7):2352-64

Date

04/01/1996

Pubmed ID

8601815

Pubmed Central ID

PMC3327288

Scopus ID

2-s2.0-0029885161   289 Citations

Abstract

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.

Author List

Wade PR, Chen J, Jaffe B, Kassem IS, Blakely RD, Gershon MD

Author

Iris S. Kassem MD, PhD Associate Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Antibody Specificity
Base Sequence
Biological Transport
Carrier Proteins
Colon
Epithelium
Guinea Pigs
Immunohistochemistry
Intestinal Mucosa
Intestine, Small
Membrane Glycoproteins
Membrane Transport Proteins
Molecular Sequence Data
Myenteric Plexus
Nerve Tissue Proteins
Neurons
Peristalsis
Rats
Sensitivity and Specificity
Serotonin
Serotonin Plasma Membrane Transport Proteins