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. 1991 Sep;104(1):227–233. doi: 10.1111/j.1476-5381.1991.tb12411.x

Effects of lemakalim on changes in Ca2+ concentration and mechanical activity induced by noradrenaline in the rabbit mesenteric artery.

S Ito 1, J Kajikuri 1, T Itoh 1, H Kuriyama 1
PMCID: PMC1908282  PMID: 1786512

Abstract

1. Effects of (-)-cromakalim (lemakalim) on tension and Ca2+ mobilization induced by noradrenaline (NA) were investigated by measuring intracellular Ca2+ concentration ([Ca2+]i) isometric tension and production of inositol-1,4,5-trisphosphate (IP3) in smooth muscle strips of the rabbit mesenteric artery. 2. In thin smooth muscle strips, 10 microM NA produced a large phasic, followed by a small tonic increase in [Ca2+]i, which correlated well with the evoked phasic and tonic contractions, respectively. Lemakalim (0.1-10 microM) lowered the resting [Ca2+]i without a decrease in the resting tension, and also inhibited the increased [Ca2+]i and tension induced by 10 microM NA, all in a concentration-dependent manner. Glibenclamide (1 microM) inhibited these actions of lemakalim. 3. In Ca(2+)-free solution containing 2 mM EGTA, NA (10 microM) transiently increased [Ca2+]i, tension and synthesis of IP3. Lemakalim (over 0.01 microM) inhibited these actions of NA in Ca(2+)-free solution containing 5.9 mM K+, but not in Ca(2+)-free solution containing 128 mM K+. These actions of lemakalim were prevented by glibenclamide (1 microM). Lemakalim (1 microM) did not modify the increases in [Ca2+]i and tension induced by 10 mM caffeine. 4. In beta-escin-skinned strips, 10 microM NA increased [Ca2+]i in Ca(2+)-free solution containing 50 microM EGTA, 3 microM guanosine triphosphate (GTP) and 2 microM Fura 2 after the storage sites were loaded by application of 0.3 microM Ca2+ for 2 min, suggesting that Ca2+ is released from intracellular storage sites following activation of the alpha-adrenoceptor. Lemakalim (1 microM) did not inhibit the Ca2+ release from storage sites induced by NA.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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