Fujiwara S, Kuriyama H
J Pharmacol Exp Ther. 1983 May;225(2):447-55.
The effects of nicardipine on smooth muscle cells of the guinea-pig basilar artery were investigated by means of microelectrode and isometric tension recording methods. Nicardipine (1 X 10(-8) to 3 X 10(-6) M) did not modify the membrane potential and resistance of smooth muscle cells. The spike evoked by application of outward current pulse in the presence of tetraethylammonium (greater than 1 X 10(-3) M) was inhibited by 1 X 10(-9) M and was almost blocked by 3 X 10(-7) M nicardipine. Perivascular nerve stimulation evoked the excitatory junction potential which was slightly suppressed by 3 X 10(-6) M nicardipine. The contractions evoked by excess concentration of [K]0, NaCl-free solution or ATP was abolished and by 5-hydroxytryptamine was markedly inhibited in Ca-free ethylene glycol bis(beta-aminoethyl ether)N,N'-tetracetic acid-containing solution, but that induced by caffeine was only slightly inhibited. Nicardipine (greater than 3 X 10(-10) M) markedly inhibited the K-induced contraction noncompetitively as estimated from the Lineweaver-Burk's plot. The ATP-induced contractions were slightly inhibited by nicardipine (greater than 1 X 10(-8) M) to a lesser extent than the K-induced contraction. On the other hand, nicardipine (1 X 10(-6) M) had no effect on the NaCl-free-or 5-hydroxytryptamine-induced contraction. When nicardipine (1 X 10(-6) M) was applied during 2.5 mM Ca loading to muscle cells after depletion of the stored Ca, the subsequently generated caffeine-induced contraction was slightly inhibited due to inhibition of the passive Ca influx. These results indicate that nicardipine possesses a selective inhibitory action for the Ca channel, but the inhibition is limited to particular Ca influxes such as the voltage-dependent one, but not the receptor operated and NaCl-free-induced Ca influxes. This agent acts predominantly on the postjunctional muscle rather than the prejunctional nerve terminal.
采用微电极和等长张力记录方法，研究了尼卡地平对豚鼠基底动脉平滑肌细胞的作用。尼卡地平（1×10⁻⁸至3×10⁻⁶M）未改变平滑肌细胞膜电位和电阻。在四乙铵（大于1×10⁻³M）存在下，施加外向电流脉冲诱发的动作电位被1×10⁻⁹M抑制，3×10⁻⁷M尼卡地平几乎完全阻断。血管周围神经刺激诱发兴奋性接头电位，3×10⁻⁶M尼卡地平使其略有抑制。在无钙乙二醇双（β-氨基乙基醚）N，N'-四乙酸溶液中，高浓度[K]₀、无氯化钠溶液或ATP诱发的收缩被消除，5-羟色胺诱发的收缩被显著抑制，但咖啡因诱发的收缩仅略有抑制。根据Lineweaver-Burk图估计，尼卡地平（大于3×10⁻¹⁰M）非竞争性地显著抑制钾诱导的收缩。ATP诱导的收缩被尼卡地平（大于1×10⁻⁸M）轻度抑制，程度小于钾诱导的收缩。另一方面，尼卡地平（1×10⁻⁶M）对无氯化钠或5-羟色胺诱导的收缩无影响。当在储存钙耗尽后向肌肉细胞加载2.5mM钙期间应用尼卡地平（1×10⁻⁶M）时，随后产生的咖啡因诱导的收缩因被动钙内流的抑制而略有抑制。这些结果表明，尼卡地平对钙通道具有选择性抑制作用，但这种抑制仅限于特定的钙内流，如电压依赖性钙内流，而不是受体操纵和无氯化钠诱导的钙内流。该药物主要作用于接头后肌肉而非接头前神经末梢。
