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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.

ABSTRACT: 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.

SUBMITTER: Chen JJ

PROVIDER: S-EPMC6763151 | biostudies-literature | 2001 Aug

REPOSITORIES: biostudies-literature

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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.

Chen J J JJ Li Z Z Pan H H Murphy D L DL Tamir H H Koepsell H H Gershon M D MD

The Journal of neuroscience : the official journal of the Society for Neuroscience 20010801 16

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 +/+ bow ...[more]

PMID: 11487658

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Project description:Background/aimsEnterochromaffin cells (EC cells) constitute the largest population of enteroendocrine cells and release serotonin (5-HT) in response to mechanical and chemical cues of the gastrointestinal tract (GIT). How EC cells respond to altered microbiota such as due to antibiotic treatments remain poorly understood. We hypothesized that the pacemaker channel HCN2 might contribute to the regulation of EC cells functions and their responses to antibiotics-induced changes in intestinal flora.MethodsMice were given either penicillin or streptomycin or both in drinking water for 10 consecutive days. The changes in the profile of short chain fatty acids (SCFAs) in the cecum following penicillin or streptomycin treatments were tested by GC-MS. Serum 5-HT content, whole intestinal transit time, fecal water content, cecum weight and expression of HCN2 and TPH1 in cecal mucosa were measured. Ivabradine (a HCN channels blocker) was used to explore the role of HCN2 in penicillin-induced changes in 5-HT availability and intestinal motility.ResultsHCN2 immunofluorescence was detected on intestinal EC cells. Both penicillin and streptomycin caused significant reduction in total SCFAs in the cecum, with the penicillin-treated group showing greater reductions in butyrate, isobutyrate and isovalerate levels than the streptomycin group. The expression of HCN2 was increased in the mice treated with penicillin, whereas TPH1 expression was increased in the mice treated with streptomycin. Mice treated with antibiotics all had larger and heavier cecum, elevated serum 5-HT level and increased fecal water content. Besides, mice treated with penicillin had prolonged intestinal transit time. Intraperitoneal injection of Ivabradine attenuated the effect of penicillin on serum 5-HT level, cecum size and weight, intestinal motility, and fecal water content.ConclusionDisruptions of the intestinal flora structure due to oral administration of penicillin may significantly increase serum 5-HT level and inhibit intestinal motility, at least partially through up-regulating the expression of HCN2. Oral administration of streptomycin may alter 5-HT availability by up-regulating TPH1 expression thus increasing synthesis of 5-HT. Alterations of intestinal flora composition due to exposure to different antibiotics may regulate 5-HT availability and intestinal motility through different mechanisms.

Dataset Information

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.

Publications

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.

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