Localization and function of a 5-HT transporter in crypt epithelia of the 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 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.
Wade
P R
PR
Department of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, 10032, USA.
Chen
J
J
Jaffe
B
B
Kassem
I S
IS
Blakely
R D
RD
Gershon
M D
MD
D000818:Animals; D000918:Antibody Specificity; D001483:Base Sequence; D001692:Biological Transport / Q000502:physiology; D002352:Carrier Proteins / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D003106:Colon / Q000737:chemistry* / Q000166:cytology; D004848:Epithelium / Q000737:chemistry / Q000378:metabolism; D006168:Guinea Pigs; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D007421:Intestine, Small / Q000737:chemistry* / Q000166:cytology; D008562:Membrane Glycoproteins / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D009197:Myenteric Plexus / Q000166:cytology; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000737:chemistry / Q000378:metabolism; D010528:Peristalsis / Q000502:physiology; D051381:Rats; D012680:Sensitivity and Specificity; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D012701:Serotonin