A possible mechanism in the anti-anaphylactic effect of beta-adrenoceptor agonists in guinea-pig lungs.

The anaphylactic mediators, histamine and leukotrienes, stimulate arachidonic acid (AA) metabolism in the guinea-pig lungs, leading to the synthesis and release of thromboxane A2 (TxA2) and other cyclo-oxygenase products. Since TxA2 is a potent bronchoconstrictor, it is possible that the activation of AA metabolism by histamine may contribute to the pulmonary manifestations of anaphylaxis. In the present experiments, histamine-induced release of TxA2 was inhibited by mepyramine (10(-8)-10(-6) M) but not by cimetidine (5 X 10(-5) M) indicating that the release was mediated by H1-receptors. The beta-adrenoceptor agonists, fenoterol (10(-6) M) and isoprenaline (10(-6) M) inhibited the histamine-induced release of TxA2. This effect was partially reversed by propranolol. These results suggest that if histamine-induced TxA2 release is involved in guinea-pig pulmonary anaphylaxis then inhibition of this release may be a factor in the anti-anaphylactic effect of beta-adrenoceptor agonists.