Nicorandil--induced ATP release in endothelial cells of rat caudal artery is associated with increase in intracellular Ca(2+).
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.
Hashimoto
M
M
Department of Physiology, Shimane Medical University, Shimane 693-8501, Izumo, Japan. michio1@shimane-med.ac.jp
Shinozuka
K
K
Sasaki
T
T
Tanaka
N
N
Hossain
S
S
Kubota
Y
Y
Tamura
K
K
Shido
O
O
Kunitomo
M
M
D000241:Adenosine / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D018613:Microscopy, Confocal; D020108:Nicorandil / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013498:Suramin / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007211:Indoles; D014665:Vasodilator Agents; D020108:Nicorandil; D013498:Suramin; D019284:Thapsigargin; D000255:Adenosine Triphosphate; D000241:Adenosine; D005905:Glyburide; D002118:Calcium; C000543:cyclopiazonic acid