Recent advances on the importance of the serotonin transporter SERT in the rat intestine

Martel, Fátima

doi:10.1016/j.phrs.2006.04.005

Cited by 40 publications

(33 citation statements)

References 43 publications

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“…A neuronal SERT has been cloned in rats (16), guinea pigs (5), mice (3), bovines (24), and humans (25). Functionally, this transporter is Na ϩ and Cl Ϫ dependent and is inhibited by SSRIs such as fluoxetine (20). SERT has also been characterized in specialized nonneuronal cells, including platelets (2,26), pulmonary endothelium (19), and placental syncytiotrophoblasts (26).…”

mentioning

confidence: 99%

Function, expression, and characterization of the serotonin transporter in the native human intestine

Gill¹,

Pant²,

Saksena³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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Gill RK, Pant N, Saksena S, Singla A, Nazir TM, Vohwinkel L, Turner JR, Goldstein J, Alrefai WA, Dudeja PK. Function, expression, and characterization of the serotonin transporter in the native human intestine. Am J Physiol Gastrointest Liver Physiol 294: G254-G262, 2008. First published November 8, 2007 doi:10.1152/ajpgi.00354.2007.-The enteric serotonin transporter (SERT) plays a critical role in modulating serotonin availability and thus has been implicated in the pathogenesis of various intestinal disorders. To date, SERT expression and function in the human intestine have not been investigated. Current studies were designed to characterize the function, expression, distribution, and membrane localization of SERT in the native human intestine. Real-time PCR studies showed relatively higher SERT mRNA expression in the human small intestine compared with colon (ileum ϾϾ duodenum ϾϾ jejunum). Northern blot analysis revealed three mRNA hybridizing species encoding SERT (3.0, 4.9, and 6.8 kb) in the human ileum. Consistent with SERT mRNA expression, SERT immunostaining was mainly detected in the epithelial cells of human duodenal and ileal resected tissues. Notably, SERT expression was localized predominantly to the apical and intracellular compartments and was distributed throughout the crypt-villus axis. Immunoblotting studies detected a prominent protein band (ϳ70 kDa) in the ileal apical plasma membrane vesicles (AMVs) isolated from mucosa obtained from organ-donor intestine. Functional studies showed that uptake of [ 3 H]serotonin (150 nM) in human ileal AMVs was 1) significantly increased in the presence of both Na ϩ and Cl Ϫ ; 2) inhibited (ϳ50%) by the neuronal SERT inhibitor, fluoxetine (10 M) and by unlabeled 5-HT; and 3) exhibited saturation kinetics indicating the presence of a carrier-mediated process. Our studies demonstrated differential expression of SERT across various regions of the human intestine and provide evidence for the existence of a functional SERT capable of removing intraluminal serotonin in human ileal epithelial cells. serotonin uptake; serotonin transporter expression SEROTONIN (5-hydroxytryptamine, 5-HT) is a neurotransmitter and hormone that influences diverse physiological functions. About 90% of the whole body content of 5-HT is present in the gastrointestinal (GI) tract, where it plays a critical role in modulation of gut motility and fluid and electrolyte transport (10,12,28,30). The majority of 5-HT in the GI tract is synthesized and stored in secretory granules of mucosal enterochromaffin (EC) cells. EC cells continuously release small amounts of 5-HT in response to a number of chemical and mechanical stimuli (13). Because 5-HT exerts its effects via specific 5-HT receptor subtypes, a mechanism for 5-HT deactivation is necessary to prevent the receptors from desensitization. The enzymes that catabolize 5-HT, including monoamine oxidases and glucuronyl transferases, are localized intracellularly and thus require transport of 5-HT across plasma membranes (5, 31). However, 5-...

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confidence: 99%

Function, expression, and characterization of the serotonin transporter in the native human intestine

Gill¹,

Pant²,

Saksena³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Although the regional biosynthesis, release, metabolism and distribution of serotonin and localization of its diverse receptors and uptake sites are well studied in the CNS (Chojnacka-Wojcik, 1995;Kilpatrick et al, 1986;Martin & Sibson, 21008), relatively fewer studies have attempted to investigate the regional distribution of such serotonergic parameters in either the gut or the ENS of commonly laboratory animals (Gershon, 1999;Cho et al, 2006;Martel, 2006), and only scant data in limited regions of the gut is available in vomit competent species (Fukui et al, 1993;Pettersson, 1979;Endo et al, 1998). Since the premise of the revised multi-neurotransmitter theory of chemotherapy-induced immediate and delayed vomiting heavily depends on the release of serotonin from ECs, the distribution of these cells along the GIT, especially of an emetic species, is of paramount importance.…”

Section: -Hydroxytryptaminementioning

confidence: 99%

Distribution of Serotonin-immunoreactive Enterochromaffin Cells in the Gastrointestinal Tract of the Least Shrew (Cryptotis parva)

et al. 2012

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SUMMARY:Serotonin is an important neurotransmitter in the central (CNS) and peripheral (PNS) nervous systems. It is involved in a variety of physiological processes both in the gut and in the CNS. The present study examined the distribution of serotonin containing enterochromaffin cells in the gastrointestinal tract (GIT) of a vomit competent species, the least shrew. These cells were easily recognized by their globular granules stained with the H&E and serotonin immune-positive stain. The immunoreactive enterochromaffin cells (IERCs) were mainly confined to the basal portion of the glandular epithelium and were distributed throughout the shrew stomach, small and large intestine. None was found to be associated with the mucosal epithelial lining. Moreover, their distribution and count varied in different regions of the GIT suggesting specific functions for these regions. The highest concentration of IERCs was found in the colon followed by the Jejunum. Appreciable numbers of IERCs were found in the stomach especially at the esophageo-gastric junction. The gastric location of the IERCs was mainly in the basal portion of the gland. However, some IERCs were associated with the parietal cells of the stomach. Two types of IERCs were observed: One with globular secretory granules in their apical portion of the cytoplasm which were located within the glandular epithelial cells facing the glandular lumen which release their secretions into the lumen; and the second were basally located, facing the lamina propria of the mucosa. Their secretory granules were not distinct in shape, and are most probably paracrine in their mode of secretions.

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“…Serotonin can then generate a wide variety of intracellular effects as there are 16 receptor subtypes, with all but one being G protein-coupled receptors that lead to the activation of secondary messenger systems [6]. The uptake of serotonin from the extracellular space into the cell via serotonin transporters terminates serotonin receptormediated signaling [7]. Predominantly, it is the enzyme monoamine oxidase A that degrades serotonin once it is inside the cell [8].…”

Section: Introductionmentioning

confidence: 99%

The specific serotonin reuptake inhibitors sertraline and fluoxetine promote tumor growth in a mouse xenograft model of cholangiocarcinoma

McMillin

Smith

Shin

et al. 2017

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Recent advances on the importance of the serotonin transporter SERT in the rat intestine

Cited by 40 publications

References 43 publications

Function, expression, and characterization of the serotonin transporter in the native human intestine

Function, expression, and characterization of the serotonin transporter in the native human intestine

Distribution of Serotonin-immunoreactive Enterochromaffin Cells in the Gastrointestinal Tract of the Least Shrew (Cryptotis parva)

The specific serotonin reuptake inhibitors sertraline and fluoxetine promote tumor growth in a mouse xenograft model of cholangiocarcinoma

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