ARC 118925XX stimulates cation influx in bEND.3 endothelial cells.

In a previous publication when we studied the purinergic receptor with which ATP interacted in mouse brain bEND.3 endothelial cells, we observed addition of 3 μm ARC 118925XX (ARC; selective P2Y antagonist) strongly suppressed ATP-triggered Ca release, suggesting the response was mediated via P2Y receptors. We here report ARC unexpectedly promoted substantial Ca influx even when ATP-triggered Ca release was largely inhibited. Since this large Ca influx may have important pharmacological significance, we proceeded to investigate its mechanism. ARC did not trigger intracellular Ca release thus suggesting Ca influx triggered by ARC was not store-operated. ARC-triggered Ca influx could be blocked by 1 mm Ni , a general Ca channel blocker, but not by SK&F 96365, a nonselective TRP channel blocker. Unexpectedly, ARC promoted influx of Na and La , but not Mn . This is a surprising finding, since Mn is conventionally used as a Ca surrogate ion (as it permeates Ca channel), and La is classically used as a potent Ca channel antagonist. Electrophysiological examination showed ARC did not stimulate any cation currents. Therefore, ARC opened, rather than a cation channel pore, an unidentified Ca influx pathway which was Na - and La -permeable but Mn -impermeable.