Godfraind T, Dessy C, Salomone S
Laboratoire de Pharmacologie, Université Catholique de Louvain, Brussels, Belgium.
J Pharmacol Exp Ther. 1992 Oct;263(1):112-22.
The actions of L-type calcium channel blockers on the contractile response to serotonin and to K(+)-depolarization have been studied in human coronary artery and in human internal mammary artery. The effect of ketanserin indicated that in both arteries serotonin action may be related not only to 5-serotonin2 but also to other serotonin receptors. In fura-2-loaded coronary and mammary arteries, exposed to serotonin (10 microM), nisoldipine (1 microM) and verapamil (10 microM) reversed completely the increase in [Ca++] cyt but not the contraction. The Ca++ antagonist-resistant contraction was equal to 26.2 +/- 2.1% of controls (n = 57) in coronary artery and to 51.7 +/- 4.2% (n = 19) in internal mammary artery. The concentration inhibiting by 50% the tonic contraction to serotonin sensitive to calcium channels blockade was 61-fold lower in human coronary artery than in human internal mammary artery with nisoldipine, but only 3.7-fold lower with nifedipine. There was no significant difference with diltiazem and verapamil. When human coronary artery and human internal mammary artery were exposed to a 100-mM KCl depolarizing solution, their sensitivity to nisoldipine was not significantly different. Preincubation with calcium antagonists in a 40-mM KCl solution reversibly increased the inhibitory effect of nisoldipine but not that of the other calcium antagonists. Comparison of radioligand and functional data shows that inhibition by calcium antagonists of the response to both serotonin and K(+)-depolarizing solution may be related to interaction with L-type calcium channels. The results indicate that the very high sensitivity to nisoldipine of the tonic response evoked by serotonin in human coronary artery might be related to the voltage-dependence of this dihydropyridine.
在人冠状动脉和人乳内动脉中研究了L型钙通道阻滞剂对5-羟色胺和钾离子去极化引起的收缩反应的作用。酮色林的作用表明，在这两种动脉中，5-羟色胺的作用可能不仅与5-羟色胺2受体有关，还与其他5-羟色胺受体有关。在加载fura-2的冠状动脉和乳内动脉中，暴露于5-羟色胺（10微摩尔）时，尼索地平（1微摩尔）和维拉帕米（10微摩尔）可完全逆转[Ca++]细胞内浓度的升高，但不能逆转收缩。钙拮抗剂抵抗性收缩在冠状动脉中相当于对照组的26.2±2.1%（n = 57），在乳内动脉中相当于51.7±4.2%（n = 19）。对钙通道阻滞剂敏感的5-羟色胺引起的紧张性收缩被抑制50%时的浓度，在人冠状动脉中比在人乳内动脉中使用尼索地平时低61倍，但使用硝苯地平时仅低3.7倍。地尔硫卓和维拉帕米没有显著差异。当人冠状动脉和人乳内动脉暴露于100毫摩尔氯化钾去极化溶液时，它们对尼索地平的敏感性没有显著差异。在40毫摩尔氯化钾溶液中用钙拮抗剂预孵育可可逆地增加尼索地平的抑制作用，但不增加其他钙拮抗剂的抑制作用。放射性配体和功能数据的比较表明，钙拮抗剂对5-羟色胺和钾离子去极化溶液反应的抑制可能与与L型钙通道的相互作用有关。结果表明，人冠状动脉中5-羟色胺引起的紧张性反应对尼索地平的极高敏感性可能与这种二氢吡啶的电压依赖性有关。
