Cloning and expression of the mouse serotonin transporter

Chang, Albert S.; Chang, Sharon M.; Starnes, Diane M.; Schroeter, Sally; Bauman, Andrea L.; Blakely, Randy D.

doi:10.1016/s0169-328x(96)00172-6

Cited by 107 publications

(67 citation statements)

References 22 publications

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“…27) On the other hand, some reports indicated that serotonin reuptake transporter did not exist on liver tissue. 28,29) ] i rise and death in human oral cancer cells. 31) Therefore, SSRIs and SNRIs may induce cell injury in HepG2 cells through the different biological activities that appear to be unrelated to its serotonin reuptake inhibition.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the Anti-tumor Effects of Selective Serotonin Reuptake Inhibitors as Well as Serotonin and Norepinephrine Reuptake Inhibitors in Human Hepatocellular Carcinoma Cells

Kuwahara

Yamada

Egashira

et al. 2015

Biological & Pharmaceutical Bulletin

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The anti-tumor effects of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) on several types of cancer cells have been reported. However, comparison of the anti-tumor effects of these drugs on human hepatocellular carcinoma (HepG2) cells has not been studied. We compared the anti-tumor effects of four SSRIs and two SNRIs on HepG2 cells. SSRIs and duloxetine dose-dependently decreased cell viability. Milnacipran had no effect on cell viability. The half-maximal inhibitory concentration was lower in the order of: sertraline, paroxetine, duloxetine, fluvoxamine, escitalopram, and milnacipran. Exposure to sertraline (2 µM) significantly increased caspase-3/7 activity. These results suggest that, of the agents tested here, sertraline had the highest sensitivity to HepG2 cells, and activation of the caspase pathway is involved in the anti-tumor effects of sertraline in HepG2 cells.Key words selective serotonin reuptake inhibitor; anti-tumor effect; sertraline; serotonin and norepinephrine reuptake inhibitor; human hepatocellular carcinoma cell Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third most common cause of cancerbased death.

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Section: Discussionmentioning

confidence: 99%

Comparison of the Anti-tumor Effects of Selective Serotonin Reuptake Inhibitors as Well as Serotonin and Norepinephrine Reuptake Inhibitors in Human Hepatocellular Carcinoma Cells

Kuwahara

Yamada

Egashira

et al. 2015

Biological & Pharmaceutical Bulletin

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“…The mouse 5-HTT cDNA sequence encodes a protein of 630 amino acids which contains twelve potential transmembrane domains [39]. Real-time RT-PCR analysis demonstrated a much higher level of expression of the 5-HTT in MLO-Y4 cells compared to MC3T3-E1 osteoblastic cells and the B14 rat neuronal cell line.…”

Section: Discussionmentioning

confidence: 99%

Serotonin transporter and receptor expression in osteocytic MLO-Y4 cells

Bliziotes

Eshleman

Burt‐Pichat

et al. 2006

Bone

113

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“…A neuronal serotonin transporter (SERT) has been cloned in rats (Blakely et al, 1991;Hoffman et al, 1991), mice (Chang et al, 1996), bovine (Mortensen et al, 1999), and humans (Ramamoorthy et al, 1993). This transporter is sodium-and chloride-dependent and is specifically inhibited by serotonin-selective reuptake inhibitors (e.g., fluoxetine).…”

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confidence: 99%

Uptake of Serotonin at the Apical and Basolateral Membranes of Human Intestinal Epithelial (Caco-2) Cells Occurs through the Neuronal Serotonin Transporter (SERT)

Martel¹,

Monteiro²,

Lemos³

2003

J Pharmacol Exp Ther

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Serotonin plays important physiological functions at the intestinal level. However, nothing is known concerning its inactivation mechanisms in the human intestine. So, the aim of this work was to characterize the uptake of serotonin at the apical and basolateral membranes of human intestinal epithelial (Caco-2) cells. Uptake of [ 3 H]serotonin at the apical membrane of Caco-2 cells was specific and Na ϩ -, Cl Ϫ -, and potentialdependent. It was concentration dependently inhibited by several monoamines (with the following rank order of potency: serotonin Ͼ Ͼ dopamine Ն noradrenaline) and tricyclic and nontricyclic antidepressants (with the following rank order of potency: fluoxetine Ͼ desipramine Ͼ cocaine Ͼ GBR 12909). In contrast, it was not affected by corticosterone (0.01-100 M) and was only partially inhibited by decynium-22 (0.001-10 M). Transepithelial apparent permeability (P app ) to [ 3 H]serotonin in the apical-to-basolateral direction was reduced by desipramine (0.4 M) and fluoxetine (0.02 M), and it was not Na ϩ -dependent nor affected by corticosterone (100 M). Uptake of [3 H]serotonin at the basolateral membrane of Caco-2 cells was Na ϩ -dependent and reduced by desipramine (0.4 M) and fluoxetine (0.02 M), and it was not affected by corticosterone (100 M).The P app to [3 H]serotonin in the basolateral-to-apical direction was reduced by desipramine (0.4 M) and fluoxetine (0.02 M), and it was not affected by Na ϩ omission or by corticosterone (100 M). Reverse transcriptase-polymerase chain reaction indicates that mRNA of the neuronal serotonin transporter (SERT) is present in Caco-2 cells and in human small intestine. In conclusion, these results suggest that human intestinal epithelial Caco-2 cells functionally express SERT, both at their apical and basolateral cell membranes.The largest store of serotonin in the body is found in the gastrointestinal tract, corresponding to over 95% of the body's serotonin (Erspamer, 1966). Most of the gastrointestinal serotonin is contained in enterochromaffin (EC) cells of the mucosal epithelium, within which serotonin is synthesized from L-tryptophan and stored in secretory granules. Serotonin is also present in serotonergic neurons of the enteric nervous system. Several functions of enteric serotonin have been identified in the past years. First, serotonin acts as the neurotransmitter of a subset of myenteric interneurons (Wade et al., 1994). Second, serotonin contained in EC cells, being released in response to chemical or mechanical stimuli, affects gastrointestinal motility (it initiates peristaltic reflexes by acting on intrinsic sensory neurons and musculature) and intestinal electrolyte transport (it initiates secretory reflexes by acting on intrinsic sensory neurons and mucosal cells) (Engel et al., 1984;Imada-Shirakata et al., 1997). Moreover, extrinsic sensory neurons activated by serotonin initiate sensations from the bowel, which may include nausea, bloating, and pain (for review, see Gershon, 1999). Additionally, serotonin present in EC cells...

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Cloning and expression of the mouse serotonin transporter

Cited by 107 publications

References 22 publications

Comparison of the Anti-tumor Effects of Selective Serotonin Reuptake Inhibitors as Well as Serotonin and Norepinephrine Reuptake Inhibitors in Human Hepatocellular Carcinoma Cells

Comparison of the Anti-tumor Effects of Selective Serotonin Reuptake Inhibitors as Well as Serotonin and Norepinephrine Reuptake Inhibitors in Human Hepatocellular Carcinoma Cells

Serotonin transporter and receptor expression in osteocytic MLO-Y4 cells

Uptake of Serotonin at the Apical and Basolateral Membranes of Human Intestinal Epithelial (Caco-2) Cells Occurs through the Neuronal Serotonin Transporter (SERT)

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