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.
Compton
M R
MR
Seale
J P
JP
Shaw
J
J
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000707:Anaphylaxis / Q000517:prevention & control*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D005280:Fenoterol / Q000494:pharmacology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008168:Lung / Q000187:drug effects*; D008297:Male; D013929:Thromboxane B2 / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D001095:Arachidonic Acids; D005280:Fenoterol; D016718:Arachidonic Acid; D013929:Thromboxane B2; D006632:Histamine; D007545:Isoproterenol