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Title: | Involvement of organic cation transporter-3 and plasma membrane monoamine transporter in serotonin uptake in human brain vascular smooth muscle cells | Authors: | Li, RWS Yang, C Kwan, YW Chan, SW Lee, SMY Leung, GPH |
Issue Date: | 12-Feb-2013 | Source: | Frontiers in pharmacology, 12 Feb. 2013, v. 4, 14, p. 1-8 | Abstract: | The serotonin (5-HT) uptake system is supposed to play a crucial part in vascular functions by "fine-tuning" the local concentration of 5-HT in the vicinity of 5-HT2 receptors in vascular smooth muscle cells. In this study, the mechanism of 5-HT uptake in human brain vascular smooth muscle cells (HBVSMCs) was investigated. [3H]5-HT uptake in HBVSMCs was Na+-independent. Kinetic analyses of [3H]5-HT uptake in HBVSMCs revealed a Km of 50.36 ± 10.2 mM and a Vmax of 1033.61 ± 98.86 pmol/mg protein/min. The specific serotonin re-uptake transporter (SERT) inhibitor citalopram, the specific norepinephrine transporter (NET) inhibitor desipramine, and the dopamine transporter (DAT) inhibitor GBR12935 inhibited 5-HT uptake in HBVSMCs with IC50 values of 97.03 ± 40.10, 10.49 ± 5.98, and 2.80 ± 1.04 μM, respectively. These IC50 values were 100-fold higher than data reported by other authors, suggesting that those inhibitors were not blocking their corresponding transporters. Reverse transcription-polymerase chain reaction results demonstrated the presence of mRNA for organic cation transporter (OCT)-3 and plasma membrane monoamine transporter (PMAT), but the absence of OCT-1, OCT-2, SERT, NET, and DAT. siRNA knockdown of OCT-3 and PMAT specifically attenuated 5-HT uptake in HBVSMCs. It is concluded that 5-HT uptake in HBVSMCs was mediated predominantly by a low-affinity and Na+-independent mechanism. The most probable candidates are OCT-3 and PMAT, but not the SERT. | Keywords: | Monoamine transporter Organic cation transporter Serotonin Vascular smooth muscle cells |
Publisher: | Frontiers Research Foundation | Journal: | Frontiers in Pharmacology | ISSN: | 1663-9812 | DOI: | 10.3389/fphar.2013.00014 | Rights: | Copyright: © 2013 Li, Yang, Kwan, Chan, Lee and Leung. This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/), which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc. The following publication Li RWS, Yang C, Kwan YW, Chan SW, Lee SMY and Leung GPH (2013) Involvement of organic cation transporter-3 and plasma membrane monoamine transporter in serotonin uptake in human brain vascular smooth muscle cells. Front. Pharmacol. 4:14,1-8 is available at https://dx.doi.org/10.3389/fphar.2013.00014 |
Appears in Collections: | Journal/Magazine Article |
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