Reduction in basal adenylate cyclase activity during the immunologic release of histamine from guinea pig lung

Cyclic AMP has been implicated in the regulation of the immunologic release of histamine from lung and other tissues and cell types. The mechanism whereby intracellular levels of cAMP are altered during mediator release was investigated. Measurements of histamine, adenylate cyclase, and cAMP phosphodiesterase activities were made in actively and passively sensitized guinea pig lung after challenge with antigen. A transient decrease in basal adenylate cyclase activity occurred which returned to control levels after histamine release. There was no change in cAMP phosphodiesterase activity determined at substrate concentrations of 1 mM and 0.01 mM. The adenylate cyclase response did not occur under the following conditions: 1) incubation of nonsensitized lung with antigen, 2) incubation of sensitized lung with antigen in the absence of extracellular calcium, and 3) incubation of nonsensitized lung with compound 48/80. These observations indicate 1) the adenylate cyclase response and the immunologic release of histamine are intimately related, and 2) the reduction in intracellular levels of cAMP which have been reported to occur during immunologic histamine release are mediated via adenylate cyclase.