Pharmacology of histamine liberation. Cationic amphiphilic drugs and mast cells.

The effect of betaadrenoceptor blocking drugs atenolol and propranolol was studied in both nonstimulated and stimulated isolated rat mast cells. Atenolol did not liberate histamine from non-stimulated mast cells, decreased spontaneous secretion, inhibited 48/80 stimulated histamine release, increased 32P incorporation into membrane phospholipids, decreased membrane fluidisation and decreased arachidonic acid liberation from membrane phospholipids of stimulated mast cells. Propranolol dose-dependently liberated histamine from nonstimulated mast cells and inhibited histamine liberation, it nonsignificantly increased membrane phospholipid turnover but significantly increased membrane fluidisation and inhibited stimulated arachidonic acid liberation in stimulated mast cells. The results indicated the interaction of atenolol and propranolol with mast cell membranes, particularly with the phospholipid bilayer, resulting in a possible inhibition of phospholipase A2 activation. Histamine liberation suggested its displacement from granule binding sites after intracellular propranolol accumulation in mast cells.