Effects of isoproterenol on histamine release induced from monodispersed guinea-pig lung cells by different secretagogues

The effects of isoproterenol on histamine release induced by specific antigen (ovalbumin), a calcium ionophore (A23187) and a phorbol ester 4β-phorbol-12β-myristate-13α-acetate (TPA) were examined using passively sensitized, monodispersed guinea-pig lung cells containing 2 to 5% mast cells. Ovalbumin evoked histamine release in a manner dependent on added calcium. Isoproterenol inhibited this release and the inhibition was not overcome by increasing the concentration of calcium. The small amount of histamine release above spontaneous release induced by ovalbumin in the absence of added calcium was not altered by isoproterenol. Incubating the cells with ovalbumin in the absence of added calcium resulted in a time-dependent desensitization of histamine release induced by subsequent exposure to calcium. Isoproterenol did not affect either the rate or the maximum mangitude of antigen desensitization. Antigen-induced histamine release at maximum densensitization was not inhibited by isoproterenol. A23187 induced histamine release in a manner dependent on added calcium. This dependency was inversely related to the concentration of A23187. Isoproterenol had no effect on either the rate or magnitude of histamine release by A23187 regardless of the concentration of added calcium. TPA evoked histamine release in a manner independent of added calcium. Isoproterenol did not alter the rate or magnitude of histamine release induced by TPA. Both forskolin (10^-5 M) and dibutyryl cyclic AMP (10^-3 M) inhibited ovalbumin-induced histamine release, but neither substance altered A23187-induced release. Forskolin also failed to alter TPA-induced histamine release. These results suggest that beta adrenergic-mediated inhibition of immunologic histamine release from guinea-pig lung cells is a result of a reduction of the selective increase in mast cell membrane calcium flux evoked by antigen-antibody interaction and that this may be a cyclic AMP-dependent effect.