Title : Distribution and functional characterization of
equilibrative nucleoside transporter-4 , a novel cardiac adenosine transporter activated at acidic pH. Adenosine plays multiple roles in the efficient functioning of the heart by regulating coronary blood flow, cardiac pacemaking, and contractility
Abstract :
- Previous studies have implicated the equilibrative nucleoside transporter family member equilibrative nucleoside transporter-1 ( ENT1 ) in the regulation of cardiac adenosine levels
- We report here that a second member of this family, ENT4 , is also abundant in the heart, in particular in the plasma membranes of ventricular myocytes and vascular endothelial cells but, unlike ENT1 , is virtually absent from the sinoatrial and atrioventricular nodes
- Originally described as a monoamine/organic cation transporter, we found that both human and mouse ENT4 exhibited a novel, pH-dependent adenosine transport activity optimal at acidic pH (apparent K(m) values 0.78 and 0.13 mmol/L, respectively, at pH 5.5) and absent at pH 7.4
- In contrast, serotonin transport by ENT4 was relatively insensitive to pH. ENT4-mediated nucleoside transport was adenosine selective, sodium independent and only weakly inhibited by the classical inhibitors of equilibrative nucleoside transport, dipyridamole, dilazep, and nitrobenzylthioinosine
- We hypothesize that ENT4 , in addition to playing roles in cardiac serotonin transport, contributes to the regulation of extracellular adenosine concentrations, in particular under the acidotic conditions associated with ischemia
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