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KCI등재 학술저널

Pharmacological Evidence that Cromakalim Inhibits Ca<SUP>2&#8290;</SUP> Release from Intracellular Stores in Porcine Coronary Artery

Pharmacological Evidence that Cromakalim Inhibits Ca<SUP>2&#8290;</SUP> Release from Intracellular Stores in Porcine Coronary Artery

<P> In the present study, it was aimed to further indentify the intracellular action mechansm of cromakalim and levcromakalim in the porcine coronary artery. In intact porcine coronary arterial strips loaded with fura-2/AM, acetylcholine caused an increase in intracellular free Ca<SUP>2&#8290;</SUP> ([Ca<SUP>2&#8290;</SUP>]<SUB>i</SUB>) in association with a contraction in a concentration-dependent manner. Cromakalim (1 &#12557;M) caused a reduction in acetylcholine-induced increased [Ca<SUP>2&#8290;</SUP>]<SUB>i</SUB> not only in the mormal physiological salt solution (PSS) but also in Ca<SUP>2&#8290;</SUP>-free PSS (containing 1 mM EGTA). In the skinned strips prepared by exposure of tissue to 20 &#12557;M &#12546;-escin, inositol 1,4,5-trisphosphate (IP<SUB>3</SUB>) evoked an increase in [Ca<SUP>2&#8290;</SUP>]<SUB>i</SUB>, but it was without effect on the intact strips. The IP<SUB>3</SUB>-induced increase in [Ca<SUP>2&#8290;</SUP>]<SUB>i</SUB> was inhibited by cromakalim by 78% and levcromakalim by 59% (1 &#12557;M, each). Pretreatment with glibenclamide (a blocker of ATP-sensitive K<SUP>&#8290;</SUP> channels, 10 &#12557;M) and apamin (a blocker of small conductance Ca<SUP>2&#8290;</SUP>-activated K<SUP>&#8290;</SUP> channels, 1 &#12557;M) strongly blocked the effect of cromakalim and levcromakalim. However, charybdotoxin (a blocker of large conductance Ca<SUP>2&#8290;</SUP>-activated K<SUP>&#8290;</SUP> channels, 1 &#12557;M) was without effect. In addition, cromakalim inhibited the GTP<SUB>&#12547;</SUB>S (100 &#12557;M, nonhydrolysable analogue of GTP)-induced increase in [Ca<SUP>2&#8290;</SUP>]<SUB>i</SUB>. <P> Based on these results, it is suggested that cromakalim and levcromakalim exert a potent vasorelaxation, in part, by acting on the K<SUP>&#8290;</SUP> channels of the intracellular sites (e.g., sarcoplasmic reticulum membrane), thereby, resulting in decrease in release of Ca<SUP>2&#8290;</SUP> from the intracellular storage site.

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