Dual effect of dihydropyridines on 45 Ca uptake induced by the K + —channel blocker 4‐aminopyridin on mast cells

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 45 Ca 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 45 Ca uptake. Pretreatment of mast cells with DHP prior to 4‐aminopyridin stimulation inhibited or stimulated 45 Ca 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 45 Ca uptake. These results demonstrate a diversity of pharmacological effects of DHP on mediator secretion and 45 Ca uptake in mast cells and throw into question their only properties as Ca ++ antagonists.