EVIDENCE THAT ONLY ONE TYPE OF BETA-ADRENERGIC-RECEPTOR MEDIATES INHIBITION OF ANTIGEN-INDUCED HISTAMINE-RELEASE FROM GUINEA-PIG MINCED LUNG

  • 1 January 1984
    • journal article
    • research article
    • Vol. 229  (2) , 391-398
Abstract
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 [xamoterol fumarate], had no effect at concentrations up to 10-5 M. The .beta.-1 selective agonist RO363 [1-(3,4-dimethoxy phenylethyl amino)-3-(3,4-dihydroxyphenoxy)-2-propanol)oxalate] 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. The potency of sulfonterol relative to isoproterenol changed with antigen concentration. The .beta. antagonists propranolol 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. Practolol, a cardioselective antagonist, did not antagonize the ability of isoproterenol or RO363 to inhibit histamine release. The Kb value for propranolol, but not butoxamine, was decreased by extending the incubation period to 120 min. Evidently, a single population of receptors of the .beta.-2 subtype are involved in the adrenergic inhibition of immunologically induced histamine release from guinea-pig lung. The data also demonstrate the influence of the degree of antigen stimulus (functional antagonism) on .beta. agonist potencies and relative potencies.