常咯啉,磷酸咯啶等药物对家兔心肌脂质易化钙离子转运的影响

已知心肌细胞膜微粒体脂质(CMML)能易化钙离子从水到脂相的转运。奎尼丁能抑制这一转运过程。为进一步证明其他带含氮碱性基团的心血管药物是否也能抑制CMML易化钙离子转运过程。本文选用了常咯啉(C),磷酸咯啶(P),奎尼下(Q),乌头碱(A),调微Ⅱ号(莨菪类,T),和非含氮碱性药物成脉安(V),研究了它们对这种易化钙转运过程的影响。结果表明C,P,Q和A在30μg/ml时对这一过程的抑制均超过70％。V和T在相同浓度时抑制作用分别为37.8％和微弱作用·C,P和Q的抑制作用可能是它们治疗作用的生化基础。V和T的药理机制可能与以上药物不同。

EFFECTS OF CHANGROLIN, PYRACRINE PHOSPHATE AND THE OTHERS ON THE LIPID-FACILITATED TRANSPORT OF CALCIUM IONS IN CARDIAC MUSCLE OF RABBIT

Previous studies have shown that the lipids extracted from cardiac muscle cell membranes resemble those similarly extracted from skeletal muscle cell membranes in their ability to facilitate the transport of calcium ions from an aqueous to a lipidsolvent phase, and quinidine sulfate inhibits this lipid-facilitated transport of ionized calcium.In this study, we examined the effect of some cardiovascular drugs with alkaline group (cation),including Changrolin, Pyracrine phosphate, Aconidine, Quinidine, TaoWie-Ⅱ (Hyoseyamine), and calcium channel blocker-Verapamil, on the transport of calcium ions in membrane extract of cardiac muscle cell.The rabbit heart membrane-microsomal fraction was extracted with 1.5ml of CHCl3:CH3OH (2:1) per mg of membrane-microsomal protein.The reaction mixture of 0.3μci of 45Ca2+ in 1ml of Ringer's solution with or without added drugs and 2ml of CHCl3:CH3OH (2:1) lipid extract were kept in a water bath 2ml at 37℃,after 15 min of vigorous mixing, the two phase were separated.The radio-activityof chloroform phase was determined in a liquid scintllaton spectrometer.The incubation of Ringer's solution containing 45Ca2+ with flank CHCl3:CH3OH (2:1) solution gave negative result of 45Ca2+ in the chloroform phase.The inclusion of lipids extracted from the cell membrane-microsomal fraction caused an accumulation of 8. 8 ×0.5μmol/L Ca2+ in the chloroform phase.The addition of drug to the reaction mixture inhibited the lipid-facilitated transport of calcium ions from Ringer's solution into the chloroform phase.The percentage inhibition varied according to the concentration of the added drug.At the 30μg/ml concentration,Changrolin, Pyracrine phosphate, Aeonitine, Quindine showed over 70% of inhibition, which were even higher than the inhibitory effect (37.8) of verapamil. However, the TaoWie-Ⅱ had only slight inhibition. The mechanisms of the action of those alkaline (cation) drugs might be different. Many investigations have demonstrated that the action of quinidine on cardiac muscle may involve a change in the system responsible for the transport of sodium through the surface membrane.Feinstein suggested that the divalent cations and anesthetic drugs react with phosphate groups of phospholipoproteins lining the pores of cell membranes in such a way that the influx of sodium ions through these pores is impeded.It is possible that the interaction of the alkaline drugs with the lipid fraction as demonstrated above may provide a clue for the mechanism of producing a changed semipermeability as the basis for their therapeutic action.