Effects of formoterol (BD 40A), a beta-adrenoceptor stimulant, on isolated guinea-pig lung parenchymal strips and antigen-induced SRS-A release in rats.
Formoterol was evaluated for its inhibitory effects on tissue tonus of the isolated guinea-pig lung parenchymal (peripheral airways) and tracheal (central airways) strips and on antigen-induced release of slow reactive substance of anaphylaxis (SRS-A) in the rat. Relaxant effects of formoterol in both parenchymal and tracheal strips were dose-dependent and were of similar potency. Formoterol was 44 and 100 times more potent than isoproterenol and salbutamol, respectively, in relaxing the parenchymal preparation. Propranolol, butoxamine and atenolol antagonized the relaxation of the parenchymal strips by formoterol in this order of decreasing potency; their slopes of regression line of the Schild plots were 0.809, 0.975 and 0.676, respectively. The inhibitory effect of intraperitoneally administered formoterol on (mouse) IgE-mediated SRS-A release in rat passive peritoneal anaphylaxis was 40 and 12200 times, respectively, more potent than those of salbutamol and disodium cromoglycate (DSCG). This action was antagonized by pretreatment with propranolol. In contrast to DSCG which dose-dependently inhibited histamine release, neither formoterol nor salbutamol was effective in inhibiting the release. The results indicate that formoterol potently relaxes the peripheral airways through stimulating the beta 2-adrenoceptors selectively as is the case in the central airways and that it significantly inhibits IgE-mediated SRS-A release through beta-adrenoceptor stimulation.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000403:Airway Resistance / Q000187:drug effects; D000420:Albuterol / Q000494:pharmacology; D000707:Anaphylaxis / Q000503:physiopathology; D000818:Animals; D004205:Cromolyn Sodium / Q000494:pharmacology; D004983:Ethanolamines / Q000494:pharmacology*; D000068759:Formoterol Fumarate; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008168:Lung / Q000187:drug effects*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000378:metabolism*; D014132:Trachea / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D013189:SRS-A; D011433:Propranolol; D007545:Isoproterenol; D004205:Cromolyn Sodium; D000420:Albuterol; D000068759:Formoterol Fumarate