RT Journal Article
SR Electronic
T1 Maintenance of Serotonin in the Intestinal Mucosa and Ganglia of Mice that Lack the High-Affinity Serotonin Transporter: Abnormal Intestinal Motility and the Expression of Cation Transporters
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 6348
OP 6361
DO 10.1523/JNEUROSCI.21-16-06348.2001
VO 21
IS 16
A1 Jason J. Chen
A1 Zhishan Li
A1 Hui Pan
A1 Dennis L. Murphy
A1 Hadassah Tamir
A1 Hermann Koepsell
A1 Michael D. Gershon
YR 2001
UL http://www.jneurosci.org/content/21/16/6348.abstract
AB The enteric serotonin reuptake transporter (SERT) has been proposed to play a critical role in serotonergic neurotransmission and in the initiation of peristaltic and secretory reflexes. We analyzed potential compensatory mechanisms and enteric function in the bowels of mice with a targeted deletion of SERT. The guts of these animals were found to lack mRNA encoding SERT; moreover, high-affinity uptake of 5-HT into epithelial cells, mast cells, and enteric neurons was present in the SERT +/+ bowel but absent in the SERT −/− bowel. However, both the SERT +/+ gut and the −/− gut expressed molecules capable of transporting 5-HT, but with affinities and selectivity much lower than those of SERT. These included the dopamine transporter (DAT) and polyspecific organic cation transporters OCT-1 and OCT-3. DAT and OCT immunoreactivities were present in both the submucosal and myenteric plexuses, and the OCTs were also located in the mucosal epithelium. 5-HT was found in all of its normal sites in the SERT −/− bowel, which contained mRNA encoding tryptophan hydroxylase, but no 5-HT was present in the blood of SERT −/− animals. Stool water and colon motility were increased in most SERT −/− animals; however, the increase in motility (diarrhea) occasionally alternated irregularly with decreased motility (constipation). The watery diarrhea is probably attributable to the potentiation of serotonergic signaling in SERT −/− mice, whereas the transient constipation may be caused by episodes of enhanced 5-HT release leading to 5-HT receptor desensitization.