Inhibition of histamine release from dispersed human lung and tonsillar mast cells by nicardipine and nifedipine.
Calcium entry blocking drugs attenuate antigen-induced bronchoconstriction in asthma which is mast cell mediated. We have investigated the effects of two calcium uptake blockers, nicardipine and nifedipine on histamine secretion from human mast cells dispersed from lung and tonsillar tissue. Mast cells were activated for secretion with anti-human IgE or calcium ionophore, A23187. Nicardipine and nifedipine caused a concentration-related inhibition of IgE-dependent histamine release from both lung (IC30 10 microM and 4.4 microM) and tonsillar (IC30 21 microM and 47 microM) mast cells. Nicardipine and nifedipine also inhibited mast cell histamine release induced by A23187 with IC30 values of 14 microM and 67 microM for lung and 15 microM and 30 microM for tonsillar mast cells. In the absence of drugs, increasing the extracellular calcium concentrations from 0.2 to 5 mM caused a concentration related increase in IgE-dependent histamine release from tonsillar mast cells. Both nicardipine and nifedipine (50 microM) displaced the concentration-effect curve to the right. Nicardipine (0.01-100 microM) caused a concentration related inhibition of rat kidney histamine methyltransferase activity used in the radioenzymatic assay of histamine (ki of 7.5-12 microM) whereas nifedipine was only a weak inhibitor. Nicardipine also interfered with the spectrofluorimetric assay after exposure to ultraviolet light. These observations demonstrate that nicardipine and nifedipine inhibit IgE-dependent and ionophore stimulated mediator secretion from human mast cells. The lack of stimulus-related specificity and the high drug concentrations required suggest that classical calcium channel blockade is not responsible for inhibition of mast cell mediator release. Furthermore, we suggest that inhibition of mast cell mediator release is unlikely to be the mechanism by which these drugs alleviate asthma.
Y Y
YY
Kim
S T
ST
Holgate
M K
MK
Church
D000001:Calcimycin / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism* / Q000528:radiation effects; D008780:Methyltransferases / Q000378:metabolism; D009529:Nicardipine; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014066:Palatine Tonsil / Q000378:metabolism; D014466:Ultraviolet Rays
D002121:Calcium Channel Blockers; D007073:Immunoglobulin E; D000001:Calcimycin; D009529:Nicardipine; D008780:Methyltransferases; D009543:Nifedipine