Serotonin transporter and receptor expression in osteocytic MLO-Y4 cells.
Neurotransmitter regulation of bone metabolism has been a subject of increasing interest and investigation. We reported previously that osteoblastic cells express a functional serotonin (5-HT) signal transduction system, with mechanisms for responding to and regulating uptake of 5-HT. The clonal murine osteocytic cell line, MLO-Y4, demonstrates expression of the serotonin transporter (5-HTT), and the 5-HT(1A), and 5-HT(2A) receptors by real-time RT-PCR and immunoblot analysis. Immunohistochemistry using antibodies for the 5-HTT, and the 5-HT(1A) and 5-HT(2A) receptors reveals expression of all three proteins in both osteoblasts and osteocytes in rat tibia. 5-HTT binding sites were demonstrated in the MLO-Y4 cells with nanomolar affinity for the stable cocaine analog [(125)I]RTI-55. Imipramine and fluoxetine, antagonists with specificity for 5-HTT, show the highest potency to antagonize [(125)I]RTI-55 binding in the MLO-Y4 cells. GBR-12935, a relatively selective dopamine transporter antagonist, had a much lower potency, as did desipramine, a selective norepinephrine transporter antagonist. The maximal [(3)H]5-HT uptake rate in MLO-Y4 cells was 2.85 pmol/15 min/well, with a K(m) value of 290 nM. Imipramine and fluoxetine inhibited specific [(3)H]5-HT uptake with IC(50) values in the nanomolar range. 5-HT rapidly stimulated PGE(2) release from MLO-Y4 cells; the EC(50) for 5-HT was 0.1 muM, with a 3-fold increase seen at 60 min. The rate-limiting enzyme for serotonin synthesis, tryptophan hydroxylase, is expressed in MLO-Y4 cells as well as osteoblastic MC3T3-E1 cells. Thus, osteocytes, as well as osteoblasts, are capable of 5-HT synthesis, and express functional receptor and transporter components of the 5-HT signal transduction system.[1]References
- Serotonin transporter and receptor expression in osteocytic MLO-Y4 cells. Bliziotes, M., Eshleman, A., Burt-Pichat, B., Zhang, X.W., Hashimoto, J., Wiren, K., Chenu, C. Bone (2006) [Pubmed]
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