赛庚啶对大鼠心肌细胞膜［~3H］－d－cis－硫氮卓酮结合部位的影响

EFFECTS OF CYPROHEPTADINE ON [3H]-D-CIS-DILTIAZEM BINDIND SITES IN CARDIAC SARCOLEMMAL MEMBRANES OF RATS

苯并噻嗪类钙通道阻滞剂［３Ｈ］－ｄ－ｃｉｓ－硫氮酮能以一种特异和可饱和的方式与离体大鼠心肌细胞膜结合，其ＫＤ值和Ｂｍａｘ分别为８４ｎｍｏｌ·Ｌ－１和０．２７９ｐｍｏｌ·ｍｇｐｒｏｔｅｉｎ－１。非标记的硫氮酮和赛庚啶均能完全抑制这种结合，其Ｋｉ值分别为１０２ｎｍｏｌＬ－１和５．５ｕｍｏｌ·Ｌ－１。上述结果证实在大鼠心肌细胞膜上也存有［３Ｈ］－硫氮酮受体，同时还提示赛马庚啶对心肌细胞膜的钙通道阻滞作用可能与作用于心肌细胞膜［３Ｈ］硫氮酮受体有关。

The characteristics of[3H]-d-cis-diltiazem binding sites in cardiac sarcolemmalmembrane of rats and effects of diltiazem and cyproheptadine(Cyp ) on these binding sites werestudied.[3H]-d-cis-diltiazem,a benzothiazepine calcium antagonist, was shown to be bound to crudecardiac sarcolcmmal membrane of rats in a specific and saturable manner with a KD= 84 nmol·L-1and a receptor site density (maximum binding) of 0. 279 pmol· mg protein-1. Diltiazem and Cyp,an antiserotonin-antihistaminic agent with calcium channel blocker activity, was found to completelyinhibit the binding with Ki values of 102 nmol. L-1 and5.5umol·L-1, respectively. The resultsdemonstrate the existence of[3H]-d-cis-diltiazem binding sites in cardiac sarcolemmal membrane ofrats and also suggest that the calcium channel blocker activity of Cyp on cardiac cells may be related,at least in part, to its binding to the [3H]-d-cis-diltiazem binding sites in cardiac sarcolemmalmembranes.