Kim Y Y, Holgate S T, Church M K
Br J Clin Pharmacol. 1985 May;19(5):631-8. doi: 10.1111/j.1365-2125.1985.tb02690.x.
Calcium entry blocking drugs attenuate antigen-induced bronchoconstriction in asthma which is mast cell mediated. We have investigated the effects of two calcium uptake blockers, nicardipine and nifedipine on histamine secretion from human mast cells dispersed from lung and tonsillar tissue. Mast cells were activated for secretion with anti-human IgE or calcium ionophore, A23187. Nicardipine and nifedipine caused a concentration-related inhibition of IgE-dependent histamine release from both lung (IC30 10 microM and 4.4 microM) and tonsillar (IC30 21 microM and 47 microM) mast cells. Nicardipine and nifedipine also inhibited mast cell histamine release induced by A23187 with IC30 values of 14 microM and 67 microM for lung and 15 microM and 30 microM for tonsillar mast cells. In the absence of drugs, increasing the extracellular calcium concentrations from 0.2 to 5 mM caused a concentration related increase in IgE-dependent histamine release from tonsillar mast cells. Both nicardipine and nifedipine (50 microM) displaced the concentration-effect curve to the right. Nicardipine (0.01-100 microM) caused a concentration related inhibition of rat kidney histamine methyltransferase activity used in the radioenzymatic assay of histamine (ki of 7.5-12 microM) whereas nifedipine was only a weak inhibitor. Nicardipine also interfered with the spectrofluorimetric assay after exposure to ultraviolet light. These observations demonstrate that nicardipine and nifedipine inhibit IgE-dependent and ionophore stimulated mediator secretion from human mast cells. The lack of stimulus-related specificity and the high drug concentrations required suggest that classical calcium channel blockade is not responsible for inhibition of mast cell mediator release. Furthermore, we suggest that inhibition of mast cell mediator release is unlikely to be the mechanism by which these drugs alleviate asthma.
钙通道阻滞剂可减轻哮喘中由肥大细胞介导的抗原诱导的支气管收缩。我们研究了两种钙摄取阻滞剂尼卡地平和平痛新对从肺和扁桃体组织中分离出的人肥大细胞组胺分泌的影响。用抗人IgE或钙离子载体A23187激活肥大细胞以进行分泌。尼卡地平和硝苯地平对肺（IC30分别为10 microM和4.4 microM）和扁桃体（IC30分别为21 microM和47 microM）肥大细胞的IgE依赖性组胺释放产生浓度依赖性抑制。尼卡地平和硝苯地平也抑制了A23187诱导的肥大细胞组胺释放，肺肥大细胞的IC30值分别为14 microM和67 microM，扁桃体肥大细胞的IC30值分别为15 microM和30 microM。在无药物情况下，将细胞外钙浓度从0.2 mM增加到5 mM会导致扁桃体肥大细胞的IgE依赖性组胺释放呈浓度依赖性增加。尼卡地平和硝苯地平（50 microM）均使浓度-效应曲线右移。尼卡地平（0.01 - 100 microM）对用于组胺放射酶法测定的大鼠肾脏组胺甲基转移酶活性产生浓度依赖性抑制（ki为7.5 - 12 microM），而硝苯地平只是一种弱抑制剂。尼卡地平在暴露于紫外光后也会干扰荧光分光光度测定。这些观察结果表明，尼卡地平和硝苯地平抑制人肥大细胞的IgE依赖性和离子载体刺激的介质分泌。缺乏刺激相关的特异性以及所需的高药物浓度表明，经典的钙通道阻滞并非抑制肥大细胞介质释放的原因。此外，我们认为抑制肥大细胞介质释放不太可能是这些药物缓解哮喘的机制。
