The Role of the Cyclic AMP System in Inflammation: An Introduction
The first suggestion that agents that could increase the intracellular level of cyclic AMP were capable of inhibiting inflammatory responses was in 1968 with the demonstration that the catecholamines and methylxanthines could inhibit antigen-induced, IgE-mediated histamine release from human leukocyte preparations (1). It had been shown, to be sure, as early as 1937, that epinephrine could inhibit histamine release from the lung of a sensitized guinea pig (2). These experiments, however, were carried out long before the cyclic AMP system was discovered by Sutherland and his colleagues. It was their research, demonstrating the effects of the cyclic AMP system in secretory reactions, that led us to undertake this experimentation. A number of different lines of evidence, generated in the early sixties, convinced us that IgE-mediated histamine release from human basophils, and similar reactions in other systems, represented secretory reactions (3, 4). It was natural at that point to ask whether cyclic AMP controlled this reaction as it did other secretory phenomenon. The fact that it appeared to do so was not a surprise; what was surprising was that an increased level of cyclic AMP turned off the response in this system rather than facilitating it, which was the common experience at that time. Obviously, this is no longer so novel.
KeywordsHistamine Release Histamine Receptor Human Basophil cAMP System Inhibit Histamine Release
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