title: Serotonin and fluoxetine receptors are expressed in enamel organs and LS8 cells and modulate gene expression in LS8 cells.
abstract: The selective serotonin re-uptake inhibitor (SSRI) fluoxetine is widely used in the treatment of depression in children and fertile women, but its effect on developing tissues has been sparsely investigated. The aim of this study was to investigate if enamel organs and ameloblast-derived cells express serotonin receptors that are affected by peripherally circulating serotonin or fluoxetine. Using RT-PCR and western blot analysis we found that enamel organs from 3-d-old mice and ameloblast-like cells (LS8 cells) express functional serotonin receptors, the rate-limiting enzyme in serotonin synthesis (Thp1), as well as the serotonin transporter (5HTT), indicating that enamel organs and ameloblasts are able to respond to serotonin and regulate serotonin availability. Fluoxetine and serotonin enhanced the alkaline phosphatase activity in the cell culture medium from cultured LS8 cells, whereas the expression of enamelin (Enam), amelogenin (Amel), and matrix metalloproteinase-20 (MMP-20) were all significantly down-regulated. The secretion of vascular endothelial growth factor (VEGF), monocyte chemotactic protein 1 (MCP-1), and interferon-inducible protein 10 (IP-10) was also reduced compared with controls. In conclusion, enamel organs and ameloblast-like cells express functional serotonin receptors. Reduced transcription of enamel proteins and secretion of vascular factors may indicate possible adverse effects of fluoxetine on amelogenesis.
authors.affiliation: Department of Biomaterials, Faculty of Dentistry, University of Oslo, Oslo, Norway.
authors.forename: Elisabeth A
authors.initials: EA
authors.lastname: Riksen
authors.forename: Astrid K
authors.initials: AK
authors.lastname: Stunes
authors.forename: Anne
authors.initials: A
authors.lastname: Kalvik
authors.forename: Björn I
authors.initials: BI
authors.lastname: Gustafsson
authors.forename: Malcolm L
authors.initials: ML
authors.lastname: Snead
authors.forename: Unni
authors.initials: U
authors.lastname: Syversen
authors.forename: Ståle P
authors.initials: SP
authors.lastname: Lyngstadaas
authors.forename: Janne E
authors.initials: JE
authors.lastname: Reseland
mesh_terms: D000469:Alkaline Phosphatase / Q000032:analysis / Q000187:drug effects; D000565:Ameloblasts / Q000187:drug effects*; D053523:Amelogenin / Q000032:analysis / Q000187:drug effects; D000818:Animals; D018929:Cell Culture Techniques; D002460:Cell Line; D018932:Chemokine CCL2 / Q000032:analysis / Q000187:drug effects; D054357:Chemokine CXCL10 / Q000032:analysis / Q000187:drug effects; D003470:Culture Media; D003746:Dental Enamel Proteins / Q000032:analysis / Q000187:drug effects; D004658:Enamel Organ / Q000187:drug effects*; D005473:Fluoxetine / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000032:analysis / Q000187:drug effects; D053519:Matrix Metalloproteinase 20 / Q000032:analysis / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D011985:Receptors, Serotonin / Q000032:analysis / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000032:analysis / Q000187:drug effects; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013054:Spectrophotometry, Atomic; D014365:Tryptophan Hydroxylase / Q000032:analysis / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000187:drug effects
chemical_list: D000469:Alkaline Phosphatase; D053523:Amelogenin; D018932:Chemokine CCL2; D054357:Chemokine CXCL10; D003470:Culture Media; D003746:Dental Enamel Proteins; D005473:Fluoxetine; D007770:L-Lactate Dehydrogenase; D053519:Matrix Metalloproteinase 20; D011985:Receptors, Serotonin; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D014365:Tryptophan Hydroxylase; D042461:Vascular Endothelial Growth Factor A; C490890:Ambn protein, mouse; C491768:Ccl2 protein, mouse; C493231:Slc6a4 protein, mouse; C038456:tuftelin; C467480:vascular endothelial growth factor A, mouse; C487801:Tph1 protein, mouse; C507113:Mmp20 protein, mouse