Biological effects and cyclic AMP production during molecular histocompatibility antigen and beta-adrenoceptor interactions.

It has been previously demonstrated that murine alloimmune IgG, while specifically recognizing class I histocompatibility (HC) antigens (Ag) of cardiac tissue, was able to increase the contractile tension and frequency of spontaneously beating isolated preparations and that this effect involved beta adrenoceptor activation. Here we show that beta 1 adrenoceptors of murine myocardium are the only stimulatory cardiac receptors that could interact with alloantibodies (allo-Ab), as the specific blockade of stimulant receptors did not alter alloimmune IgG mechanical effect on atria. Moreover, beta adrenergic participation in the phenomenon was confirmed by the isoproterenol-like increase of cardiac cAMP levels in cardiac preparations pre-treated with allo-Ab, that could be blocked by the beta antagonist propranolol. We also show that alloimmune IgG fixation to myocardium could be specifically interfered with by beta- and beta 1-selective blockers. All these data point to the fact that the mechanism whereby alloimmune IgG may trigger a beta adrenergic biological effect is through a direct molecular interaction between HC Ag and adenylate cyclase-coupled beta adrenoceptors.