Besch H R, Watanabe A M
J Pharmacol Exp Ther. 1977 Aug;202(2):354-64.
A tritium-labeled derivative of quinidine (D3HQ) was used to assess binding and effect of this drug on isolated membrane preparations from myocardium. D3HG bound to sarcoplasmic reticulum vesicles (SRV) and diminished both Ca++ binding and Ca++ uptake activity. Binding of more than 19 nmol of D3HQ were required to displace 1 nmol of Ca++. Dual-wavelength spectrophotometric methods for monitoring the alterations in Ca++ binding showed that D3HQ depressed maximal Ca++ binding and hastened the onset of Ca++ release from Ca++-loaded SRV, but did not alter the maximal rate of Ca++ release. D3HG also diminished Ca++ sequestration by isolated cardiac mitochondria but the level of D3HQ binding did not correlate with the degree of inhibition. Binding of D3HQ to Na+, K+-adenosine triphosphatase also occurred to a limited extent and a partial inhibition of enzyme activity resulted. A reciprocal relationship between D3HQ binding and a decrease in functional activity of the subcellular membrane systems could be demonstrated only for SRV. The results suggest that cinchona alkaloids might affect myocardial contractility by their effects on Ca++ handling by SRV.
使用奎尼丁的一种氚标记衍生物（D3HQ）来评估该药物对分离的心肌膜制剂的结合作用及效果。D3HG与肌浆网囊泡（SRV）结合，并降低了钙离子结合及钙离子摄取活性。置换1纳摩尔钙离子需要超过19纳摩尔的D3HQ结合。用于监测钙离子结合变化的双波长分光光度法表明，D3HQ降低了最大钙离子结合量，并加速了钙离子从钙离子负载的SRV中释放的起始，但未改变钙离子释放的最大速率。D3HG还减少了分离的心脏线粒体对钙离子的摄取，但D3HQ的结合水平与抑制程度无关。D3HQ与钠钾 - 三磷酸腺苷酶的结合也在有限程度上发生，并导致酶活性部分受到抑制。仅对于SRV，可证明D3HQ结合与亚细胞膜系统功能活性降低之间存在反比关系。结果表明，金鸡纳生物碱可能通过其对SRV处理钙离子的影响来影响心肌收缩力。
