Effects of a dihydropyridine calcium antagonist and agonist on human basophil histamine release.

Abstract

Calcium influx is important to basophil histamine release, and even though a cromolyn-binding protein has been proposed to constitute a Ca2+ channel, the pathway of Ca2+ influx or involvement of a Ca2+ channel in this process has yet to be established. We evaluated the effects of a dihydropyridine antagonist, nitrendipine, and agonist, BAY k 8644, on human basophil histamine release. Nitrendipine inhibited ragweed antigen E-dependent basophil histamine release in a dose-dependent fashion with a 50% inhibitory dose of 3.7 (+/- 1.1) X 10(-6) mol/L, and maximal inhibition of histamine release (41.8% +/- 7.1%) was achieved with 1.0 X 10(-5) mol/L nitrendipine. Increased extracellular concentrations of Ca2+ reduced nitrendipine inhibition of histamine release. In contrast, the Ca2+ agonist, BAY k 8644, enhanced antigen E-dependent histamine release with an ED50 value of 5.0 (+/- 1.1) X 10(-6) mol/L. BAY k 8644 by itself, however, did not cause basophil histamine release nor did it enhance histamine release to the calcium ionophore A23187. Further, when the effects of BAY k 8644 on basophil histamine release were evaluated in the presence of nitrendipine, the enhancing action of BAY k 8644 was diminished in a competitive fashion. Therefore, even though these compounds act at specific Ca2+ channels in other tissues, our data do not establish either the presence of such channels in the IgE-dependent histamine release process of basophils or the mechanism of action for dihydropyridines in basophil histamine secretion.(ABSTRACT TRUNCATED AT 250 WORDS)