It has been shown that histamine and bradykinin as well as catecholamines and methylxanthins elevate cellular cyclic AMP levels. In the present investigation, the inhibitory effects of bradykinin or histamine on the induction of immediate type and delayed type allergic skin reactions were studied in comparison with those of isoproterenol and theophylline. The results obtained were as follows
1) The 48 hr heterologous passive cutaneous anaphylaxis (PCA) in the rat using mouse IgE antiserum was employed as the experimental model of the immediate type allergic skin test.
(2) Bradykinin (10^-4-10^-6 M) or histamine (10^-3-10^-5 M) was intracutaneously injected to the site of antiserum. Ninety minutes after the injection PCA was tested and it was found that PCA manifestation was remarkably suppressed.
(3) The 48 hr heterologous PCA in the rat was also suppressed by the administration of isoproterenol (10^-3-10^-6 M).
(4) The delayed type skin reaction was tested in the guinea pig immunized with the emulsion of orthochlorbenzoyl boivin gamma globulin (OCB-BGG) and complete Freund adjuvant. In order to know the effects of bradykinin (10^-4M), histamine (10^-3′ M), isoproterenol (10^-4M) and theophylline (10^-4 M) on the skin reaction, these drugs were intracutaneously injected together with antigen (OCB-BGG)
(5) Bradykinin or histamine significantly suppressed the delayed type skin reaction in the guinea pig. H₂ antagonist completely blocked the suppressive effect of bradykinin or histamine, whereas H₁ antagonist scarecely blocked it.
(6) The inhibitory effect of isoproterenol or theophylline on the delayed type skin reaction in the immunized guinea pig was observed, but the effect was not dependent on dose.
(7) The results obtained suggest that the inhibition of the cellular immunological response by bradykinin, histamine, isoproterenol or theophylline may depends on the elevation of cellular cAMP through 1-12 receptors of lymphocytes.