Pharmacological Evidence that Cromakalim Inhibits Ca<SUP>2⁢</SUP> Release from Intracellular Stores in Porcine Coronary Artery
Pharmacological Evidence that Cromakalim Inhibits Ca<SUP>2⁢</SUP> Release from Intracellular Stores in Porcine Coronary Artery
- Byung Yong Rhim Sun Hwa Hong Chi Dae Kim Won Suk Lee Ki Whan Hong
- 대한생리학회-대한약리학회
- The Korean Journal of Physiology & Pharmacology
- 제1권 제1호
- 등재여부 : KCI등재
- 1997.01
- 27 - 34 (8 pages)
<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⁢</SUP> ([Ca<SUP>2⁢</SUP>]<SUB>i</SUB>) in association with a contraction in a concentration-dependent manner. Cromakalim (1 ㄍM) caused a reduction in acetylcholine-induced increased [Ca<SUP>2⁢</SUP>]<SUB>i</SUB> not only in the mormal physiological salt solution (PSS) but also in Ca<SUP>2⁢</SUP>-free PSS (containing 1 mM EGTA). In the skinned strips prepared by exposure of tissue to 20 ㄍM ㄂-escin, inositol 1,4,5-trisphosphate (IP<SUB>3</SUB>) evoked an increase in [Ca<SUP>2⁢</SUP>]<SUB>i</SUB>, but it was without effect on the intact strips. The IP<SUB>3</SUB>-induced increase in [Ca<SUP>2⁢</SUP>]<SUB>i</SUB> was inhibited by cromakalim by 78% and levcromakalim by 59% (1 ㄍM, each). Pretreatment with glibenclamide (a blocker of ATP-sensitive K<SUP>⁢</SUP> channels, 10 ㄍM) and apamin (a blocker of small conductance Ca<SUP>2⁢</SUP>-activated K<SUP>⁢</SUP> channels, 1 ㄍM) strongly blocked the effect of cromakalim and levcromakalim. However, charybdotoxin (a blocker of large conductance Ca<SUP>2⁢</SUP>-activated K<SUP>⁢</SUP> channels, 1 ㄍM) was without effect. In addition, cromakalim inhibited the GTP<SUB>㄃</SUB>S (100 ㄍM, nonhydrolysable analogue of GTP)-induced increase in [Ca<SUP>2⁢</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>⁢</SUP> channels of the intracellular sites (e.g., sarcoplasmic reticulum membrane), thereby, resulting in decrease in release of Ca<SUP>2⁢</SUP> from the intracellular storage site.