Qu Y L, Takamizawa C, Sugiyama K, Maruyama K, Hattori K, Watanabe K, Nagatomo T
Department of Pharmacology, Niigata College of Pharmacy, Japan.
Zhongguo Yao Li Xue Bao. 1995 Jul;16(4):289-93.
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- oxadiazolyl-5-yl)-4-(3-nitrophenyl) pyridine-5-carboxylate).
The membrane-enriched fractions were prepared from rat brain. The brain membranes were preincubated with nifedipine (10 nmol L-1), amlodipine (1 mumol 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 Kd and Bmax values of the membrane fractions pretreated with the drugs were determined by Scatchard analysis.
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.
Amlodipine and SM-6586 are Ca2+ antagonists which dissociate slowly from the Ca2+ channel in membranes.
检测用氨氯地平预处理的大鼠脑膜中[3H]伊拉地平结合位点的密度变化，并与硝苯地平和(+)SM-6586（1,4-二氢-2,6-二甲基-3-(3-(N-苄基-N-甲基氨基甲基)-1,2,4-恶二唑-5-基)-4-(3-硝基苯基)吡啶-5-羧酸甲酯）进行比较。
从大鼠脑制备富含膜的组分。将脑膜与硝苯地平（10 nmol/L）、氨氯地平（1 μmol/L）和SM-6586（1 nmol/L）预孵育45分钟，或不添加拮抗剂，然后洗涤并离心3次。在孵育介质中用[3H]伊拉地平对其进行测定。通过Scatchard分析确定用药物预处理的膜组分的Kd和Bmax值。
硝苯地平诱导的[3H]伊拉地平结合位点的阻断通过洗涤得以逆转，从而能够观察到特异性结合位点的低值。另一方面，氨氯地平和SM-6586引起的阻断不易逆转。然而，这些药物的Kd值之间未发现显著差异。
氨氯地平和SM-6586是Ca2+拮抗剂，它们从膜中的Ca2+通道缓慢解离。
