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

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.