Mast cell receptors controlling histamine release: influences on the mode of action of drugs used in the treatment of adverse drug reactions.

In drug-induced allergic diseases of the immediate type (anaphylactic and anaphylactoid reactions), the primary target cells are tissue mast cells, which discharge their granular content upon interaction with different secretagogues (immunological releasers; histamine liberators) on specific plasma membrane receptors. Experiments are reviewed here which report that IgE-mediated histamine release from mast cells, and the secretion of histamine induced by non-immunological secretagogues (dextran; compound 48/80; acetylcholine) are blocked by beta-adrenoceptor and H2-receptor agonists, their inhibiting effect being surmountable by beta-adrenoceptor blocking drugs and by anti-H2-antihistamines. Specific radioligands ([3H]-dihydroalprenolol; [3H]-cimetidine) binding to rat mast cell membranes points to the possibility that inhibition of histamine release is brought about by the activation of mast cell beta-adrenoceptors and H2-receptors. Drugs used in therapy of anaphylactic or anaphylactoid reactions may act either on tissue receptors, competing with released mediators, or by inhibiting the release of allergic mediators from mast cells, on activation of specific receptors located in mast cell plasma membranes.