Pharmacologic Control of Allergic Histamine Release in Vitro: Evidence for an Inhibitory Role of 3′,5′-Adenosine Monophosphate in Human Leukocytes

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Abstract
The ability of catecholamines, prostaglandins and histamine to stimulate accumulation of 3′,5′-adenosine monophosphate (cyclic AMP) in human leukocytes correlated well with their ability to inhibit antigen-induced release of histamine from cells of allergic donors in vitro. In both systems the order of potency of adrenergic agents was characteristic of the beta-receptor (isoproterenol τ epinephrine τ norepinephrine τ phenylephrine), and prostaglandins E1 and E2 were equally active, while PGF1α produced no effect. A beta-adrenergic blocking agent, propranolol, specifically antagonized the effect of catecholamines on both cyclic AMP and histamine release, but had no effect against either the prostaglandins or histamine. These results strongly support the hypothesis that cyclic AMP acts as a “second messenger” in leukocytes to inhibit allergic release of histamine. Like dibutyryl cyclic AMP and the methylxanthines, all agents which increase synthesis of leukocyte cyclic AMP act to block antigenic histamine release at an early stage of the release process, although the precise mechanism has not yet been defined.

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