Calcium antagonists in experimental asthma.

Abstract

Introduction The release of histamine from mast cells following antigen-IgE binding is dependent on increased permeability to calcium ions through specific calcium channels in the cell membrane. The secretion of mediators from mast cells can also be initiated by calcium ionophore A23187, or by direct injection of calcium ions into the cell, even in the absence of antigen. The release of mediators is thus regulated by extra and intracellular levels of calcium ions (Mongar & Foreman, 1979). It has been proposed that the anti-allergic drug sodium cromoglycate may prevent mediator release by blocking the calcium channels of mast cells (Foreman & Garland, 1976). Calcium ions are also involved in smooth muscle contraction and other secretory processes. Thus, inhibition of calcium ion influx should be beneficial in allergic asthma which involves both the increased bronchial hyper-reactivity and the release of mast cell mediators. Verapamil and nifedipine selectively inhibit calcium ion influx across the cell membrane. In vitro, verapamil and nifedipine have been reported to inhibit anaphylaxis in the airway smooth muscle (Weiss & Markowicz, 1981) and also to prevent the release of platelet-activating factor and slow reacting substance of anaphylaxis from human neutrophils (Cerrina et al., 1981). In addition, both these drugs suppress calcium-dependent smooth muscle excitation and contraction, and are also capable of neutralizing the vasoconstrictor effect of histamine, serotonin, ergotamine and acetylcholine (Fleckenstein-Griin et al., 1978). We have investigated the effect of verapamil and nifedipine in exercise-induced asthma and also on the histamine bronchial reactivity in patients with allergic asthma.