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

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) and 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, whereas concentrations of 10(-12)-10(-6) M did not significantly inhibit the secretion. 4-Aminopyridin, 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.

Amiloride‐dependent transport is the main mechanism implicated in sodium iinflux regulation in rat mast cells

“…We have previously shown that both pleural and peritoneal mast cells have no specific sodium channel (Vieytes et al, 1991b) and that cation fluxes may take place through common channels (Eleno et al, 1988). Also, the existence of a Na+/K+ pump which contributes to sodium efflux was demonstrated in rat mast cells.…”

Effect of ion composition on the changes in membrane potential induced with several stimuli in rat mast cells

“…Ouabain does not cause any appreciable change on the membrane potential confirming that the Na+/K+ ATPase pump is not directly implicated in maintaining the resting potential in these cells (Mohr and Fewtrell, 1987b). RBL cells or basophils appear to be different to many secretory cells, since they fail to secrete when they are depolarized in high potassium medium (Eleno et al, 1988;Mohr and Fewtrell, 1987a).…”

K-Channel Blocking Drugs Induce Histamine Release and ⁴⁵Ca Uptake in Isolated Mast Cells

“…The total activity added to each test tube was 500±30x 103 dpm. The method used has been de scribed previously [7]; briefly, a layer of immersion oil was placed at the bottom of Akes cylindroconical polyethylene tubes (500 pi). A suspension of purified mast cells was carefully decanted onto this layer and incubated for 20 min at 37 °C in BSS without protein.…”

“…Sensi tized mast cells secrete a wide variety of inflammatory mediators upon cross-linking of plasma membrane IgE receptors. Attempts to determine how mast cell secretion may be regulated have included the identifi cation of several receptors and N a+-, K+-, and Ca2+-specific ionic channels [4,7,12,16,25], How ever, it is not fully understood how the activation of the receptors of IgE initiates the exocytosis. There is little and conflicting information about the electrophysiological properties of mast cells.…”