NMDA receptors are involved in dithiothreitol-induced hypothermia

The effect of nicorandil, an ATP-sensitive K(+) channel opener, on the level of intracellular Ca(2+) (Ca(2+)](i)) and on ATP release in endothelial cells of the rat caudal artery was examined using a fluorescent confocal microscopic imaging system and high-performance liquid chromatography (HPLC) with fluorescent detection, respectively. Nicorandil significantly increased Ca(2+)](i) and the overflow of ATP and its metabolites. The former reaction was abolished in the absence of extracellular Ca(2+), but it did not change in the presence of thapsigargin or cyclopiazonic acid. The increase in the overflow of ATP and Ca(2+)](i) induced by nicorandil was markedly suppressed by glibenclamide, an ATP-sensitive K(+) channel blocker. The increase of Ca(2+)](i) induced by nicorandil was significantly and inversely correlated with the level of intracellular ATP in the endothelial cells, suggesting that activation of ATP-sensitive K(+) channels by nicorandil increases Ca(2+) influx in endothelial cells. The increase of Ca(2+)](i) might be associated with ATP release.