Lüllmann H, Mohr K
Br J Pharmacol. 1987 Mar;90(3):567-74. doi: 10.1111/j.1476-5381.1987.tb11207.x.
The binding of [3H]-nitrendipine to intact, electrically driven isolated left atria of guinea-pigs was investigated over the concentration range 10(-10) M to 3 X 10(-5) M. A high affinity binding site saturable in the nM range as found in ventricular homogenates could not be detected. Instead the accumulation of nitrendipine in intact atria was found to be proportional to the concentration from 10(-10) M to 10(-6) M; beyond 10(-6) M the binding started to become saturated. Nitrendipine was highly accumulated in atrial tissue. The cell:medium ratios amounted to about 120 in the range from 10(-10) M to 10(-6) M. The concentration-response curve for the negative inotropic action of nitrendipine yielded an ED50 of 3 X 10(-7) M, thus lying within the range of concentration-proportional accumulation. The reduction of the contractile force proceeded faster (t1/2 less than 10 min) than the uptake process t1/2 approximately 40 min) suggesting that it is the binding of nitrendipine into a superficial compartment, which interferes with the excitation-contraction coupling. The results suggest that the high concentration of nitrendipine present in hydrophobic cellular compartments such as the plasmalemma might be involved in its pharmacological action.
研究了[3H]-尼群地平在10(-10) M至3×10(-5) M浓度范围内与豚鼠完整的、电驱动的离体左心房的结合情况。在心室匀浆中发现的纳摩尔范围内可饱和的高亲和力结合位点未被检测到。相反,发现尼群地平在完整心房中的蓄积与10(-10) M至10(-6) M的浓度成正比;超过10(-6) M时,结合开始饱和。尼群地平在心房组织中高度蓄积。在10(-10) M至10(-6) M范围内,细胞与培养基的比例约为120。尼群地平负性肌力作用的浓度-反应曲线的ED50为3×10(-7) M,因此处于浓度成正比蓄积的范围内。收缩力的降低比摄取过程(t1/2约为40分钟)更快(t1/2小于10分钟),这表明是尼群地平与一个浅表区室的结合干扰了兴奋-收缩偶联。结果表明,疏水细胞区室(如质膜)中存在的高浓度尼群地平可能与其药理作用有关。