Mycophenolic acid inhibits the degranulation of rat peritoneal mast cells.
The effect of mycophenolic acid (MPA), a potent inhibitor of inosine monophosphate dehydrogenase, on the degranulation of rat peritoneal mast cells (RMC) was studied. RMC were pretreated for 48 hr with 0.1-10 microM MPA before the cells were sensitized with IgE and triggered with specific Ag. The net amount of [3H]5-HT released from granules was decreased by 44 and 32% with 1 and 10 microM MPA treatment, respectively. MPA inhibition of degranulation was completely reversed by the addition of 30 microM guanosine to the incubation medium. There was no difference in the apparent number or affinity of IgE binding sites between control and MPA-treated RMC. MPA pretreatment also had no effect on the IgE receptor-mediated production of PGD2 in RMC. These results suggest that depletion of intracellular GTP pools by MPA can disrupt the signaling between the IgE receptor and the secretory granules and that, under these same conditions, the release and metabolism of arachidonic acid are unaffected.
Institute of Immunology and Biological Sciences, Syntex Research, Palo Alto, California 94304.
M A
MA
Mulkins
M
M
Ng
R A
RA
Lewis
D000818:Animals; D001666:Binding Sites, Antibody; D015550:Cell Degranulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors*; D008407:Mast Cells / Q000187:drug effects*; D009173:Mycophenolic Acid / Q000494:pharmacology*; D010529:Peritoneal Cavity / Q000166:cytology; D015230:Prostaglandin D2 / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000032:analysis; D015398:Signal Transduction / Q000187:drug effects
D012701:Serotonin; D007168:IMP Dehydrogenase; D009173:Mycophenolic Acid; D015230:Prostaglandin D2