Effect of Misoprostol on Histamine Secretion from Isolated Rat and Human Mast Cells and Basophils

Misoprostol was found to be an extremely potent inhibitor of immunologically induced histamine release from mast cells isolated from both the human colonic mucosa and submucosa/muscle. The dose-inhibition curves were bell shaped, with IC(50) values in the range 0.1--1 nM. The compound was relatively selective for these cell types. It was less active against rat peritoneal mast cells, which again exhibited a bell-shaped dose-inhibition curve, but with a maximal inhibition of only about 30%, and human basophil leucocytes, where the inhibition was progressive with an IC(50) of similar1 &mgr;M. Very high concentrations of misoprostol (greater-than-or-equal5 &mgr;M) induced histamine release from all of the cell types examined. Insofar as the colonic mast cells may represent the two human mast cell phenotypes so far identified (MC(T) and MC(TC)), these data suggest that the drug may have therapeutic applications in human allergic and inflammatory diseases in which these cells are involved.