A comparison of the potency of selective L-calcium channel blockers in human coronary and internal mammary arteries exposed to serotonin

T Godfraind, C Dessy and S Salomone

Laboratoire de Pharmacologie, Universite Catholique de Louvain, Brussels, Belgium.

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.

Volume 263, Issue 1, pp. 112-122, 10/01/1992
Copyright © 1992 by American Society for Pharmacology and Experimental Therapeutics

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