Cardioprotective Effects of 9-Hydroxyellipticine on Ischemia and Reperfusion in Isolated Rat Heart

The Japanese Journal of Pharmacology

Noriko Ogiku²  Munekazu Shigekawa¹  Takeshi Matsumoto²  Kazuhiko Saeki²  Ichiro Obi²  Toshiaki Imagawa³ 

[1] Department of Molecular Physiology, National Cardiovascular Center Research Institute;Discovery Research Laboratory, Tanabe Seiyaku Co.;Division of Chemistry, Biochemistry Graduate School of Science, Hokkaido University

关键词: Ryanodine receptor;    9-Hydroxyellipticine;    Arrhythmia;    Ischemia;    Reperfusion;   

DOI  :  10.1254/jjp.89.21

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(25)Cited-By(6)We determined the effect of 9-hydroxyellipticine (9HE) on ryanodine receptor (RyR) and cardiac function after global ischemia in isolated rat hearts. The binding of [3H]-ryanodine in rabbit cardiac sarcoplasmic reticulum was displaced by 9HE in a biphasic manner corresponding to the two sites model with IC50 values of 6.1 μM and 55 mM. The increase of the intracellular Ca2+ concentration induced by caffeine in CHO cells expressing cardiac-type RyR was suppressed by 9HE in a concentration-dependent manner. Pretreatment of the heart with 9HE decreased the total duration of reperfusion-induced ventricular fibrillation (VF) and delayed the onset of VF. There was also a significant recovery of contractile force of ischemic hearts following 9HE. Unlike nifedipine, an L-type Ca2+-channel blocker, 9HE did not suppress the contraction of rat papillary muscles. Thus, 9HE exerts the cardioprotective effects against ischemia/reperfusion injury without changing hemodynamic indices.

【 授权许可】

Unknown