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PMID:11487658
| Citation |
Chen, JJ, Li, Z, Pan, H, Murphy, DL, Tamir, H, Koepsell, H and Gershon, MD (2001) 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. J. Neurosci. 21:6348-61 |
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| 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. |
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| Keywords |
Animals; Carrier Proteins/genetics; Carrier Proteins/metabolism; Constipation/physiopathology; Diarrhea/physiopathology; Dopamine Plasma Membrane Transport Proteins; Enteric Nervous System/cytology; Enteric Nervous System/metabolism; Epithelial Cells/metabolism; Ganglia/metabolism; Gastrointestinal Motility/physiology; Heterozygote; Homozygote; Intestinal Mucosa/metabolism; Mast Cells/metabolism; Membrane Glycoproteins/deficiency; Membrane Glycoproteins/genetics; Membrane Proteins/genetics; Membrane Proteins/metabolism; Membrane Transport Proteins; Mice; Mice, Knockout; Nerve Tissue Proteins; Neurons/metabolism; Organ Specificity; Organic Cation Transport Proteins; Organic Cation Transporter 1; Physical Stimulation; RNA, Messenger/metabolism; Serotonin/metabolism; Serotonin/pharmacokinetics; Serotonin Plasma Membrane Transport Proteins |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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