Possible role of organic cation transport-3 in serotonin uptake in human brain vascular smooth muscle cells

Abstract

Serotonin (5HT) is a vasoconstrictor. It has been reported that 5HT can be taken up by vascular smooth muscle cells of rat aortas through the serotonin transporters (SERT). 7KLV +7XSWDNHPHFKDQLVPSOD\VDFUXFLDOUROHLQ¿QH WXQLQJWKHDYDLODELOLW\RI +7DW its cognate receptors. However, it is unclear if SERT or other transporters are responsible for the 5HT uptake in vascular smooth muscle cells of human resistance arteries. The aim of this work was to characterize the 5HT uptake in human brain vascular smooth muscle cells (HBVSMCs). The [3 H]5HT uptake in HBVSMCs was increased with time and was saturable with a Michaelis-menten constant of 50.36 ± 10.2 mM. The [3 H]5HT uptake was enhanced when the extracellular medium was changed alkaline. Moreover, the [3 H]5HT XSWDNHZDVUHVLVWDQWWRFLWDORSUDP D6(57LQKLELWRU XSWR ȝ0 EXWLWFRXOGEHLQKLELWHG by citalopram at higher concentrations (nearly 40% inhibition by 1 mM). Tetraammonium (TEA, at 1 mM) and 1-methy-4-phenylpyridinium (MPP, at 1 mM), which are substrates of organic cation transporters (OCTs), inhibited 5HT uptake by 17 and 26%, respectively. The ORZDI¿QLW\RI +7WUDQVSRUW S+GHSHQGHQFHDQGLQKLELWLRQE\RUJDQLFFDWLRQVDUHW\SLFDO characteristics of OCTs. In addition, the results of RT-PCR demonstrated the presence of mRNA of OCT-3, but the absence of OCT-1, OCT-2, organic anion transporters (OATs) and SERT. Therefore, we suggest that the 5HT uptake in HBVSMCs is different from that in rat aorta. It is partly mediated by OCT-3, but does not involve SERT.