氨氯地平抑制大鼠脑膜与[~3H]伊拉地平结合的密度(英文)

Residual inhibition in density of [~3H]isradipine binding sites in rat brain membrane pretreated with amlodipine

目的:研究硝苯地平、氨氯地平和(+)SM-6586预处理过的大鼠脑膜与[~3H]伊拉地平观察结合密度的变化.方法:用大鼠脑膜,该脑浆膜与硝苯地平(10 nmol L^(-1)),氨氯地平(1μmol L^(-1)),SM-6586(1 nmol L^(-1))以及不加拮抗剂分别预保温45 min,离心,所得沉淀用缓冲液清洗,3次后与[~3H]伊拉地平一起保温,通过Scatchard解析求出用钙拮抗剂预处理后膜成分的K_d和B_(max)值.结果:硝苯地平对[~3H]伊拉地平取代位置的拮抗可以通过清洗而减弱,特殊取代显示出很低的值.但通过氨氯地平和SM-6586拮抗后,在同样条件下拮抗不易被减弱.以上这些药物的K_d值都没有明显的变化.结论:氨氯地平和SM-6586对脑膜中钙通道拮抗的分解过程是缓慢的.

To test changes in the density of [3H] isradipine binding sites in rat brain membrane pretreated with amlodipine and to compare with those of nifedipine and ( + ) SM-6586 (methyl 1, 4-dihydro-2, 6-dimethyl-3- (3-(N-benzyl-N-methylaminomethyl)-1,2,4-oxadia-zolyl-5-yl )-4-( 3-nitrophenyl ) pyridine-5-car-boxylate). METHODS: The membrane-enriched fractions were prepared from rat brain. The brain membranes were preincubated with nifedipine (10 nmol L-1)> amlodipine (1 umol L-1) and SM-6586 (1 nmol L-1) or with no antagonists added for 45 min, and washing and centrifugation were performed 3 times. They were assayed with [3H]isradipine in incubation media. The Kt and Bmax values of the membrane fractions pretreated with the drugs were determined by Scatchard analysis. RESULTS: The blockage of the [3H]isradipine binding sites induced by nifedipine was reversed by washing, enabling the low values of the specific binding sites to be observed. The blockages by amlodipine and SM-6586, on the other hand, were not readily reversed. No significant difference was found ,however , between in the Kd walues of these drugs. CONCLUSION: Amlodipine and SM-6586 are Ca2+ antagonists which dissociate slowly from the Ca2+ channel in membranes.