Mast Cell in Disease and its Pharmacologic Regulation

Abstract

The factors regulating the magnitude of histamine-mediated reactions in the skin need to be elucidated if we are to devise a rational therapy for urticaria. Attempts to prevent biosynthesis of histamine in vivo have proved unrewarding. Depletion of histamine stores in skin by repeated provocation of release until a state of tolerance has been reached has proved a useful procedure in patients with cold urticaria, but because of its inconvenience it requires a high degree of motivation. Attempts to moderate histamine secretion by mast cells, for example, by drugs that increase cyclic AMP, including isoproterenol and theophylline, have not met with success. Doxantrazole, a systemically administered compound with actions resembling the better known disodium cromoglycate, has been effective in suppressing histamine release evoked by cold in patients with cold urticaria, but there has been a puzzling discrepancy between clinical response and reduction in histamine release. Rate of enzymic histamine degradation may be an important factor in determining the magnitude of histamine-mediated reactions in skin. Degradation of histamine in human skin takes place by N-methylation, catalyzed by N-methyl transferase. Blockade of histamine degradation in the guinea pig leads to amplification of the histamine-mediated passive cutaneous anaphylaxis reaction in this species. Histamine-mediated skin reactions can be modulated by blockade of vascular histamine receptors. Recently the presence of 2 sub-classes of histamine receptors, H 1 and H 2 , on human skin blood vessels, has been established. Combined treatment by classical H 1 antihistamines and H 2 antihistamines offers a possibility of more effective antihistamine treatment.