Article date: December 2000
By: Satoshi Ieiri, Katsuya Hirano, Junji Nishimura, Sachiyo Suita, Hideo Kanaide in Volume 131, Issue 8, pages 1597-1606
The mechanism of vasorelaxation induced by SR33805 was investigated by simultaneously monitoring the cytosolic Ca2+ concentration ([Ca2+]i) and force, and by determining level of myosin light chain (MLC) phosphorylation in the medial strip of the porcine coronary artery.
SR33805 inhibited the sustained increases in [Ca2+]i and force (IC50; 3.2±1.0 and 49.4±27.5 nM, respectively) induced by 118 mM K+‐depolarization. There was about a 10 fold difference in the inhibitory potency between [Ca2+]i and force.
SR33805 completely inhibited the [Ca2+]i elevation induced by a thromboxane A2 analogue, U46619 and histamine, at concentrations (1 μM) higher than those required for the complete inhibition of K+‐depolarization induced [Ca2+]i elevation.
SR33805 had no effect on the [Ca2+]i elevation induced by histamine or caffeine in the absence of extracellular Ca2+.
SR33805 caused a leftward shift of the [Ca2+]i‐force relationship of the contraction induced by cumulative application of extracellular Ca2+ during 118 mM K+‐depolarization. The relationship between [Ca2+]i and MLC phosphorylation also shifted to the left by SR33805, while the relationship between MLC phosphorylation and force remained unaffected.
In conclusion, SR33805 caused an apparent leftward shift of the [Ca2+]i‐force relationship, accompanied by a greater degree of MLC phosphorylation for a given level of [Ca2+]i. The mechanism of this leftward shift, however, still remains to be elucidated.
The mechanism of vasorelaxation induced by SR33805 was investigated by simultaneously monitoring the cytosolic Ca2+ concentration ([Ca2+]i) and force, and by determining level of myosin light chain (MLC) phosphorylation in the medial strip of the porcine coronary artery.
SR33805 inhibited the sustained increases in [Ca2+]i and force (IC50; 3.2±1.0 and 49.4±27.5 nM, respectively) induced by 118 mM K+‐depolarization. There was about a 10 fold difference in the inhibitory potency between [Ca2+]i and force.
SR33805 completely inhibited the [Ca2+]i elevation induced by a thromboxane A2 analogue, U46619 and histamine, at concentrations (1 μM) higher than those required for the complete inhibition of K+‐depolarization induced [Ca2+]i elevation.
SR33805 had no effect on the [Ca2+]i elevation induced by histamine or caffeine in the absence of extracellular Ca2+.
SR33805 caused a leftward shift of the [Ca2+]i‐force relationship of the contraction induced by cumulative application of extracellular Ca2+ during 118 mM K+‐depolarization. The relationship between [Ca2+]i and MLC phosphorylation also shifted to the left by SR33805, while the relationship between MLC phosphorylation and force remained unaffected.
In conclusion, SR33805 caused an apparent leftward shift of the [Ca2+]i‐force relationship, accompanied by a greater degree of MLC phosphorylation for a given level of [Ca2+]i. The mechanism of this leftward shift, however, still remains to be elucidated.
British Journal of Pharmacology (2000) 131, 1597–1606; doi:10.1038/sj.bjp.0703721
DOI: 10.1038/sj.bjp.0703721
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