Effect of in vivo and in vitro lovastatin treatment on mast cell activation.
The hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitor lovastatin is used to treat hyperlipidaemia. This agent prevents the isoprenylation of some proteins involved in signal transduction processes and inhibits IgE-receptor-linked mediator release from RBL-2H3 cells. In this study the effect of in vivo and in vitro administration of lovastatin on histamine release from rat peritoneal mast cells was examined. Lovastatin (4 mg/kg/day for 2 weeks) inhibited histamine release induced by concanavalin A (con A) from rat peritoneal mast cells of Hooded-Lister rats and both homozygous lean and obese Zucker rats. In contrast, release induced by antirat IgE (anti-IgE) was only significantly inhibited in cells derived from Hooded-Lister rats and that induced by compound 48/80 was not altered. Lovastatin (20 microM, 24 h, in vitro) caused a significant inhibition of the subsequent histamine release to con A, anti-IgE and compound 48/80 but not to the calcium ionophore A 23187. It is important to determine whether such inhibitory effects are also observed after the chronic, clinical administration of lovastatin and other HMG CoA reductase inhibitors.
Roche
C M
CM
Department of Clinical Biochemistry, Queen's University of Belfast, Northern Ireland.
Trimble
E R
ER
Ennis
M
M
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects*; D008148:Lovastatin / Q000494:pharmacology*; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats
D000888:Antibodies, Anti-Idiotypic; C026408:anti-IgE antibodies; D003208:Concanavalin A; D008148:Lovastatin