物种和离子对离体灌注心脏中洋地黄苷积累的影响。
Species and ionic influences on the accumulation of digitalis glycosides by isolated perfused hearts.
作者信息
Dutta S, Marks B H
出版信息
Br J Pharmacol. 1972 Nov;46(3):401-8. doi: 10.1111/j.1476-5381.1972.tb08137.x.
Abstract
- The ability of isolated perfused guinea-pig (digitalis-sensitive species) and rat (digitalis-resistant species) hearts to accumulate radio-labelled digitalis glycosides was studied in relation to the ionic composition of the perfusion medium.2. It was observed that in both species much less digoxin was accumulated than was digitoxin or proscillaridin.3. The accumulation of digoxin was markedly inhibited in a low sodium or in high potassium medium. These effects were similar, but relatively less marked, with digitoxin and proscillaridin. Calcium and magnesium removal had relatively smaller effects on the accumulation of both polar and non-polar glycosides.4. The low accumulation of all digitaloids by the rat heart in comparison to the guinea-pig heart may be due to the formation of unstable complexes between the cellular membranes in the rat heart and the various digitaloids used in this study. Although digitaloids have a reduced affinity for rat hearts and rat heart membranes in comparison to guinea-pigs, the order of the accumulation of different glycosides in both species is the same, i.e. much less with polar glycosides than with non-polar glycosides.5. It was concluded that non-polar glycosides such as digitoxin and proscillaridin demonstrate the same ion-dependent accumulation mechanism as do the more polar glycosides such as digoxin and ouabain. In addition, the non-polar glycosides possess high capacity for ion-independent binding presumably due to lipophilic interactions with membranes.
摘要
研究了离体灌注豚鼠（对洋地黄敏感的物种）和大鼠（对洋地黄耐药的物种）心脏积累放射性标记洋地黄糖苷的能力与灌注介质离子组成的关系。
观察到在这两个物种中，地高辛的积累量都比洋地黄毒苷或海葱苷元少得多。
在低钠或高钾培养基中，地高辛的积累明显受到抑制。洋地黄毒苷和海葱苷元也有类似作用，但相对不那么明显。去除钙和镁对极性和非极性糖苷积累的影响相对较小。
与豚鼠心脏相比，大鼠心脏对所有洋地黄类药物的低积累可能是由于大鼠心脏细胞膜与本研究中使用的各种洋地黄类药物形成了不稳定的复合物。尽管与豚鼠相比，洋地黄类药物对大鼠心脏和大鼠心脏膜的亲和力降低，但两种物种中不同糖苷积累的顺序是相同的，即极性糖苷的积累量远低于非极性糖苷。
得出的结论是，非极性糖苷如洋地黄毒苷和海葱苷元与极性更强的糖苷如地高辛和哇巴因表现出相同的离子依赖性积累机制。此外，非极性糖苷具有高容量的非离子依赖性结合，这可能是由于与膜的亲脂性相互作用。
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