The Immediate Allergic Response: in Vitro Action of Cyclic Amp-Active and Other Drugs on the Two Stages of Histamine Release

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Abstract
The catecholamine isoproterenol, which inhibits the in vitro allergic response, does so early in the reaction in the first or activation stage of IgE-mediated histamine release and then at concentrations 104 lower than in the whole reaction. This inhibition is markedly decreased by the beta blocker propranalol but not by the alpha blocker phentolamine. Prostaglandin E1, which like the catecholamines stimulates leukocytic adenylcyclase, similarly inhibits in the first stage. Theophylline and dibutyryl cyclic AMP also inhibit primarily in the first stage but have a small but significant inhibitory effect later in the reaction, in the second stage. The metabolic inhibitor 2-deoxyglucose, on the other hand, inhibits only in the second or histamine release stage. Diethylcarbamazine inhibits both stages equally but a concentration of 10-2 M is required for a maximal effect. The action of the cyclic AMP-active drugs early in the reaction sequence strengthens the hypothesis that this system operates as a “second messenger” in the allergic release of histamine.

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