BN3C对大鼠心肌细胞膜二氢吡啶受体的作用

Effects of BN3C on dihydropyridine receptor in cardiac sarcolemmic membranes of rats

目的研究ＢＮ３Ｃ对大鼠心肌细胞膜二氢吡啶受体的作用。方法放射性配基结合实验。结果［３Ｈ］ＰＮ２００－１１０在０．１～３．２ｎｍｏｌ·Ｌ－１范围与大鼠心肌细胞膜的特异性结合是可饱和的，其ＫＤ和Ｂｍａｘ值分别为０．８２ｎｍｏｌ·Ｌ－１和１０９．７２ｐｍｏｌ·ｇ－１Ｐｒｏ－１。当有１×１０－９ｍｏｌ·Ｌ－１ＢＮ３Ｃ存在时，其ＫＤ和Ｂｍａｘ值分别为２．０１ｎｍｏｌ·Ｌ－１和１１５．３１ｐｍｏｌ·ｇ－１Ｐｒｏ－１。ＢＮ３Ｃ、拉西地平、硝苯吡啶竞争性抑制［３Ｈ］ＰＮ２００－１１０与大鼠心肌细胞膜结合的ＩＣ５０分别为２．４×１０－９，１．５×１０－８，１．９×１０－８ｎｍｏｌ·Ｌ－１；ＫＩ值分别为１．４９，９．２２和１１．６４ｎｍｏｌ·Ｌ－１。结论ＢＮ３Ｃ可特异性地作用于［３Ｈ］ＰＮ２００－１１０的结合部位，竞争性地抑制［３Ｈ］ＰＮ２００－１１０与大鼠心肌细胞膜的结合；ＢＮ３Ｃ与受体的亲和力强于拉西地平和硝苯吡啶。

AIM To study the binding properties of BN3C on dihydropyridine receptors in cardiac sarcolemmic membranes of rats. METHODS Radioligand binding assay of PN 200 110 binding to cardiac sarcolemmic membranes of rats. RESULTS PN 200 110 was bound to cardiac sarcolemmic membranes of rats in specific and saturable manner with a dissociation constant( K D)=0 82 nmol·L -1 and maximum binding concentration( B max )=109 72 pmol·g -1 Pro, In the presence of BN3C 10 -9 mol·L -1 , K D was increased( K D=2 01 mol·L -1 ) without change in B max (115 31 pmol·g -1 Pro). The K I values of competitive inhibition of BN3C, lacidipine and nifedipine on PN200 110 binding to cardiac sarcolemmic membranes of rats were 1 49,9 22 and 11 64 nmol·L -1 ,respectively. CONCLUSIONS BN3C reduced PN 200 110 binding affinity and demonstrated a competitive interaction with [ 3H]PN200 110 binding sites. The competitive inhibition of BN3C on [ 3H]PN 200 110 binding to cardiac sarcolemmic membranes of rats was more powerful than that of lacidipine and nifedipine.