Pharmacologic Inhibition of the Antigen-Induced Release of Histamine and Slow Reacting Substance of Anaphylaxis (SRS-A) from Monkey Lung Tissues Mediated by Human IgE

Abstract

Abstract Evidence was presented that agents capable of increasing intracellular levels of cyclic adenosine 3′,5′-monophosphate (AMP) also inhibit the direct, antigen-induced and reversed-type release of histamine and slow reacting substance of anaphylaxis (SRS-A) from monkey lung fragments sensitized in vitro with human atopic serum and E myeloma protein, respectively. Beta-adrenergic agents such as isoproterenol and epinephrine, which interact with β-receptors in tissues and thus activate adenyl cyclase, inhibited the release of both chemical mediators, and this inhibition was prevented by the β-adrenergic blocking agent, propranolol. The methylxanthine, theophylline, which acts as a competitive inhibitor of cyclic AMP phosphodiesterase, also inhibited the release of both histamine and SRS-A. A marked synergism was observed when β-adrenergic agents and theophylline were used together. Finally, an alkylated derivative of cyclic AMP, dibutyryl cyclic AMP, also inhibited the release of both mediators in a dose-response fashion. Agents that increase cellular levels of cyclic AMP appeared to inhibit the release of histamine and SRS-A at some point subsequent to antigen-antibody interaction and prior to the release of the mediator and in acting at such a site permitted desensitization of the sensitized tissues by specific antigen. Diethylcarbamazine was also found to inhibit the release of both histamine and SRS-A from sensitized monkey lung tissues. This agent demonstrated a remarkable synergism with the β-adrenergic agent isoproterenol, but the inhibitory activity of diethylcarbamazine was not prevented by the β-adrenergic blocking agent propranolol.