Dexamethasone or cyclosporin A inhibits stem cell factor-dependent secretory responses of rat peritoneal mast cells in vitro.
Stem cell factor (SCF) is potent activator of degranulation of rat peritoneal mast cells in vitro and may promote mast cell activation under certain circumstances in vivo. In this study we report that the anti-inflammatory glucocorticoid dexamethasone (DEX) and the immunosuppressive cyclosporin A (CsA) are both effective inhibitors of SCF-induced degranulation of rat peritoneal mast cells in vitro, measured as release of serotonin (5-HT). Of the two drugs, DEX was the more potent with near maximal inhibition reached at 10(-8) M, whereas a graded inhibition was seen with CsA in the range 10(-8)-10(-6) M. DEX was equally effective in inhibiting the release of 5-HT induced by either SCF or anti-IgE, but was less effective in inhibiting release induced by compound 48/80 or calcium ionophore A23187. CsA produced a similar degree of inhibition of degranulation induced by SCF, anti-IgE or ionophore, but was without effect on the response to compound 48/80. Neither DEX nor CsA had any significant effect on mast cell surface expression of the SCF receptor or IgE antibody. We conclude that both DEX and CsA inhibit components of the secretion-coupling pathways that are triggered following either SCF receptor engagement or cross-linking of IgE, but that these drug differentially influence mast cell secretion induced by compound 48/80 or the calcium ionophore A23187.
Taylor
A M
AM
Department of Pharmacology and Therapeutics, University of Liverpool, UK.
Galli
S J
SJ
Coleman
J W
JW
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D007073:Immunoglobulin E / Q000378:metabolism / Q000502:physiology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007476:Ionophores / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism*; D010529:Peritoneal Cavity / Q000166:cytology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D019089:Stem Cell Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D000888:Antibodies, Anti-Idiotypic; D007166:Immunosuppressive Agents; D007476:Ionophores; D019089:Stem Cell Factor; C026408:anti-IgE antibodies; D012701:Serotonin; D007073:Immunoglobulin E; D000001:Calcimycin; D003189:p-Methoxy-N-methylphenethylamine; D003907:Dexamethasone; D016572:Cyclosporine