Histamine and its antagonists in asthma

Abstract

Histamine has been recognized as a potent effector agent in allergic responses for many years. Windaus and Vogt’ first synthesized histamine in 1907, but it was Dale and Laidlaw who originally suggested that this substance could be liberated during an anaphylactic reaction when they observed that the features of anaphylaxis could be reproduced by the intravenous injection of histamine. Best et a1.3 later demonstrated that high concentrations of histamine were present in lung tissue. The association of histamine with asthma came when Weis et a1.4 found that intravenous injection of the amine in subjects with asthma induced wheezing. Further circumstantial evidence linking histamine and asthma came when blood from subjects with asthma was demonstrated to release histamine when blood was challenged with specific antigen in vitro,‘. 6 Subsequently, several authors7. * found increased plasma histamine concentrations in subjects with asthma during exacerbation of asthma. In 1951 Schild et a1.9 described the release of histamine from lung tissue after allergen challenge and commented that this coincided with the bronchoconstriction that was induced. Histamine is found in human mast cells and basophils” and is stored in secretory granules in association with heparin proteoglycan” and a variety of other preformed mediators. In Ishizaka’~‘~ classical description of mast cell activation, histamine and the remaining granule constituents are released when antigen interacts with specific IgE FcRl receptors on the surface of the mast cell. This results in the stimulation of membrane phospholipid metabolism, followed by influx of extracellular and mobilization of intracellular calcium. This intracellular signal results in the secretion of granule constituents and the mobilization of arachidonic acid from membrane phospholipid stores. Although several authors found elevations of