Evidence that only one type of beta adrenergic receptor mediates inhibition of antigen-induced histamine release from guinea-pig minced lung.

Lungs obtained from guinea pigs actively sensitized to ovalbumin were minced and prepared for histamine release studies. The effects of selective beta adrenergic receptor agonists and antagonists on the ovalbumin dose-response curve for histamine release were quantified. Beta agonist dose-response curves for inhibiting histamine release evoked by low, medium and maximum antigen concentrations as well as for shifting the antigen dose-response curve to the right were obtained. All experiments were conducted in the presence of phenoxybenzamine, 5,8,11,14-eicosatetraynoic acid and tissues were taken from reserpine-pretreated animals. The beta agonists isoproterenol and sulfonterol inhibited antigen-induced histamine release, whereas the beta-1 selective agonist, ICI 118587, had no effect at concentrations up to 10(-5) M. The beta-1 selective agonist R0363 inhibited histamine release only at concentrations known to activate the beta-2-type receptor. The maximum responses and potencies of isoproterenol and sulfonterol were inversely related to the concentration of ovalbumin at which the response was measured. The -log molar ED50 values of isoproterenol and sulfonterol were decreased approximately 10- and 5-fold, respectively, by increasing the antigen concentration from 10(-3) to 1 mg/ml. Therefore, the potency of sulfonterol relative to isoproterenol changed with antigen concentration. The beta antagonists propranolol, butoxamine and practolol did not alter antigen-induced histamine release when incubated with the tissue for 60 min. Apparent dissociation constants (KB) for propranolol and butoxamine were independent of the concentration of antigen used to provoke histamine release.(ABSTRACT TRUNCATED AT 250 WORDS)