Effects of antihistamines on isolated rat peritoneal mast cells and on model membrane systems

We have examined the effect of a range of histamine H1- and H2-receptor agonists and antagonists on rat peritoneal mast cells. Most of the compounds had a dual action: at low concentrations they inhibited the histamine release produced by immunologic activation of the cell whereas, at higher concentrations they themselves induced a cytotoxic release of the amine. The test agents did not affect intracellular levels of cyclic AMP. In model systems the majority of the drugs had no effect, on the intergrity of artificial liposomes but did protect rat erythrocytes against osmotic shock. We then propose that these agents produce their effects on mast cells by a direct action on the cell membrane, with low concentrations becoming incorporated into the bilayer in such a way as to stabilize the structure and high concentrations disrupting the membrane and leading to cell lysis.