RT Journal Article
SR Electronic
T1 Adenosine Transport by Plasma Membrane Monoamine Transporter: Reinvestigation and Comparison with Organic Cations
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1798
OP 1805
DO 10.1124/dmd.110.032987
VO 38
IS 10
A1 Mingyan Zhou
A1 Haichuan Duan
A1 Karen Engel
A1 Li Xia
A1 Joanne Wang
YR 2010
UL http://dmd.aspetjournals.org/content/38/10/1798.abstract
AB The plasma membrane monoamine transporter (PMAT) belongs to the equilibrative nucleoside transporter family (solute carrier 29) and was alternatively named equilibrative nucleoside transporter 4. Previous studies from our laboratory characterized PMAT as a polyspecific organic cation transporter that minimally interacts with nucleosides. Recently, PMAT-mediated uptake of adenosine (a purine nucleoside) was reported, and the transporter was proposed to function as a dual nucleoside/organic cation transporter. To clarify the substrate specificity of PMAT, we comprehensively analyzed the transport activity of human PMAT toward nucleosides, nucleobases, and organic cations in heterologous expression systems under well controlled conditions. Among 12 naturally occurring nucleosides and nucleobases, only adenosine was significantly transported by PMAT. PMAT-mediated adenosine transport is saturable, pH-dependent, and membrane-potential sensitive. Under both neutral (pH 7.4) and acidic (pH 6.6) conditions, adenosine is transported by PMAT at an efficiency (Vmax/Km) at least 10-fold lower than that of the organic cation substrates 1-methyl-4-phenylpyridinium and serotonin. PMAT-mediated adenosine uptake rate was significantly enhanced by an acidic extracellular pH. However, the effect of acidic pH was not adenosine-specific but was common to organic cation substrates as well. Our results demonstrated that although PMAT transports adenosine, the transporter kinetically prefers organic cation substrates. Functionally, PMAT should be viewed as a polyspecific organic cation transporter rather than an archetypical nucleoside transporter.