title: Differential recovery of beta adrenoreceptor antagonist and agonist high affinity binding sites in the guinea-pig lung after irreversible blockade.
abstract: The recovery of guinea-pig lung beta adrenoreceptors and beta adrenergic-mediated airway responsiveness was studied after irreversible receptor blockade with bromoacetylalprenololmentane (BAAM). The antagonist receptor concentration and those receptors able to form the agonist high affinity binding state were determined by (-)-[3H]dihydroalprenolol (DHA) and [3H]hydroxybenzylisoproterenol (HBI) binding, respectively. Airway responsiveness was measured by the ability of isoproterenol infusions to shift the histamine dose-response curve for airway constriction. Twenty-four hours after a single i.p. injection of BAAM (20 mg/kg), both [3H]DHA and [3H]HBI binding were reduced by 48 to 51% without changing the KD value for either ligand. In addition, there was a complete block of airway responsiveness to isoproterenol infusion at 1 microgram/kg/min although responsiveness similar to control values was observed at a higher infusion rate (10 micrograms/kg/min). Ninety-six hours after BAAM treatment, [3H]DHA binding had recovered to the control value whereas no recovery of [3H]HBI binding or of airway responsiveness was observed. By 144 hr after injection, both [3H]HBI binding and airway responsiveness had recovered to control values. The data indicate that after irreversible blockade, the total receptor population as measured by antagonists recovers relatively quickly followed by a slower recovery of those receptors able to form the agonist high affinity binding state that parallels the recovery of airway responsiveness.
authors.forename: C A
authors.initials: CA
authors.lastname: Nelson
authors.forename: T F
authors.initials: TF
authors.lastname: Muther
authors.forename: J
authors.initials: J
authors.lastname: Pitha
authors.forename: S P
authors.initials: SP
authors.lastname: Baker
mesh_terms: D000318:Adrenergic beta-Agonists / Q000378:metabolism*; D000319:Adrenergic beta-Antagonists / Q000378:metabolism* / Q000494:pharmacology; D000526:Alprenolol / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D004082:Dihydroalprenolol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000032:analysis* / Q000502:physiology; D014316:Tritium
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D014316:Tritium; D004082:Dihydroalprenolol; C015272:hydroxybenzylisoproterenol; D006632:Histamine; C045331:bromoacetylalprenololmenthane; D000526:Alprenolol; D007545:Isoproterenol