Dual effect of dihydropyridines on 45Ca 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) 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.
Eleno
N
N
Departamento de Fisiologia, Facultad de Farmacia, Universidad de Santiago de Compostela.
Botana
L
L
Espinosa
J
J
D015761:4-Aminopyridine; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000493:pharmacokinetics*; D004095:Dihydropyridines / Q000494:pharmacology*; D005260:Female; D006636:Histamine Release / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects*; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D015737:Nisoldipine; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D000631:Aminopyridines; D004095:Dihydropyridines; D007473:Ion Channels; D015737:Nisoldipine; D015761:4-Aminopyridine; D009543:Nifedipine; D011188:Potassium; D002118:Calcium