Dual effect of dihydropyridines on45Ca uptake induced by the K+ ?channel blocker 4-aminopyridin on mast cells

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Abstract
The 1,4-dihydropyridines (DHP) are calcium antagonists and represent a new class of drugs which act by a selective inhibition of Ca++ influx through voltage-operated calcium channels. We report the effect of nifedipine (Bay A 1040), nisoldipine (Bay K 5552) ad nitrendipine (Bay E 5009) on the histamine release and on the 45Ca uptake promoted by 4-aminopyridin in mast cells. These cells treated with DHP (10−12−10−3 M) activated the secretory response in a dose-dependent manner in the range of concentrations 10−6−10−3 M did not significantly inhibit the secretion. 4-Aminopridin, a known K+-channel blocker, induced 45Ca uptake. Pretreatment of mast cells with DHP prior to 4-aminopyridin stimulation inhibited or stimulated 45Ca uptake depending on concentration; thus, concentrations of DHP below 10−12 of nitrendipine and 10−9 for nisoldipine and nifedipine were inhibitory, while higher doses potentiated 45Ca uptake. These results demonstrate a diversity of pharmacological effects of DHP on mediator secretion and 45Ca uptake in mast cells and throw into question their only properties as Ca++ antagonists.