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-HT(1A) and 5-HT(7) receptors (5-HTR(1A) and 5-HTR(7)) 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-HTR(1A) and 5-HTR(7) in these cells. In addition, both receptors are shown to modulate SERT activity; 5-HTR(1A) activation increased 5-HT uptake and 5-HTR(7) activation inhibited it. In both cases, SERT modulation might involve a cAMP/PKA pathway. Effects on SERT disappeared after long-term activation of 5-HTR(1A) and 5-HTR(7), 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.
Iceta
R
R
Department of Pharmacology and Physiology, Faculty of Veterinary Sciences, the University of Zaragoza, Miguel Servet 177, Zaragoza, Spain.
Mesonero
J E
JE
Aramayona
J J
JJ
Alcalde
A I
AI
D018938:Caco-2 Cells; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000235:genetics / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*
D012333:RNA, Messenger; D011985:Receptors, Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; C104425:serotonin 7 receptor; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases