Pharmacological modulation of platelet-activating factor (PAF) release from rabbit leucocytes. I. Role of cAMP.

Basophil-rich rabbit leucocytes sensitized by anti-horseradish peroxidase antibodies released platelet-activating factor (PAF) and histamine upon exposure to the specific antigen. This release was preceded and accompanied by a sharp decrease in the intracellular concentration of cyclic AMP. Isoproterenol, a beta-adrenergic agent, and theophylline, a phosphodiesterase inhibitor, used individually or in combination, increased the intracellular concentration of cyclic AMP and inhibited the release of both PAF and histamine. Propranolol, a beta-adrenergic blocking agent, suppressed the effect of isoproterenol on cyclic AMP level and mediator release. Dibutyryl cyclic AMP, an alkylated derivative of cyclic AMP, inhibited PAF and histamine release. These results indicate that cyclic AMP, which is known to control the release of other mediators of immediate hypersensitivity, also regulates the release of PAF. Histamine and PAF followed one another closely in all of our release or inhibition experiments, bringing more evidence for the basophil origin of PAF.