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Expression of 5-HT1A and 5-HT7 receptors in Caco-2 cells and their role in the regulation of serotonin transporter activity

100%

Iceta R., Mesonero J. E., Aramayona J. J., Alcalde A. I.

Journal of Physiology and Pharmacology

2009

tom 60

nr 1

157-164

Serotonin (5-HT) receptors are expressed in the gastrointestinal tract and play an important role in gastrointestinal activity regulation. 5-HT binding to receptors depends on 5-HT availability, which is, in part, modulated by the 5-HT transporter (SERT) expressed in enterocytes. This work concerns the expression of 5-HT1A and 5-HT7 receptors (5-HTR1A and 5-HTR7) in the human enterocyte-like Caco-2 cell line and their role in SERT activity modulation. The results demonstrate the mRNA and protein expression of 5-HTR1A and 5-HTR7 in these cells. In addition, both receptors are shown to modulate SERT activity; 5-HTR1A activation increased 5-HT uptake and 5-HTR7 activation inhibited it. In both cases, SERT modulation might involve a cAMP/PKA pathway. Effects on SERT disappeared after long-term activation of 5-HTR1A and 5-HTR7, indicating their desensitization. However, in both cases, the desensitization did not show itself to be mediated by a reduction of the amount of receptors in the membrane.

Molecular characterization and intracellular regulation of the human serotonin transporter in Caco-2 cells

100%

Iceta R., Mesonero J. E., Aramayona J. J., Alcalde A. I.

Journal of Physiology and Pharmacology

2006

tom 57

nr 1

The serotonin transporter (SERT) has shown itself to be an effective pharmacological target in the treatment of mood disorders and some kinds of gastrointestinal syndromes. Most of the molecular studies of SERT in humans have been carried out using heterologous models. In this work, we have investigated the human enterocyte-like Caco-2 cell line as a potential "in vitro" model to study the human SERT. The results show that these cells express a SERT mRNA identical to the human brain SERT, and a 70 kDa protein immunodetected using a specific antibody. The SERT activity levels in Caco-2 cells increased in correlation with the onset and maintenance of the morphological and functional differentiation of the cells. Caco-2 SERT was also shown to be a high affinity (Kt=0.216 µM) saturable, Na+-dependent transporter that was inhibited by fluoxetine (IC50=17.6 nM). In addition, SERT activity was inhibited by the intracellular modulators protein kinase C and cAMP, either after short or long-term treatment. In short, the expression and molecular characteristics of the human SERT in Caco-2 cells indicate that this cell line may be an ideal tool to study in vitro the physiology and pharmacology of human SERT.

Ograniczanie wyników

2 Journal of Physiology and Pharmacology

2 Alcalde A. I.

2 Aramayona J. J.

2 Iceta R.

2 Mesonero J. E.

1 2009

1 2006

Wyniki wyszukiwania

Expression of 5-HT1A and 5-HT7 receptors in Caco-2 cells and their role in the regulation of serotonin transporter activity

Molecular characterization and intracellular regulation of the human serotonin transporter in Caco-2 cells