(±)-[3H]epinephrine and (-)-[3H]dihydroalprenolol binding to β1- and β2-noradrenergic receptors in brain, heart, and lung membranes

D. C. U'Prichard, D. B. Bylund, S. H. Snyder

Research output: Contribution to journalArticle

Abstract

(±)-[3H]Epinephrine binds to β-receptors in calf cerebellar and rat lung membranes in the presence of 1.0 mM pyrocatechol and 1.0 μM phentolamine, with dissociation constants at 4° of 11 nM and 24 nM, respectively. (±)-[3H]Epinephrine associates to equilibrium within 20 min in both tissues, and over 50% of the binding is rapidly dissociable. Inhibition of binding by agonists and antagonists is highly stereoselective, and the structure-activity relationships of adrenergic agents in inhibiting (±)-[3H]epinephrine binding suggest an interaction with β2 type noradrenergic receptors. (-)-Isoproterenol has an apparent K(i) of 2 nM, (-)-epinephrine is 1.5 to 3 times weaker and (-)-norepinephrine is 30 to 60 times weaker. Salbutamol and terbutaline, selective β2-agonists, are potent inhibitors of binding, as are several nonspecific antagonists. Properties of the sites labeled by (±)-[3H]epinephrine in calf cerebellum and rat are closely similar. (-)-[3H]Dihydroalprenolol binding in calf cerebellum and rat lung also shows β2 characteristics. Antagonists have similar potencies in inhibiting (-)-[3H]dihydroalprenolol and (±)-[3H]epinephrine binding in both tissues, but agonists are in general more potent inhibitors of (±)-[3H]epinephrine. Sodium and lithium selectively lower the affinity of (±)-[3H]epinephrine at its binding sites and the affinities of agonists, but not antagonists, at the (-)-[3H]dihydroalprenolol site. Specific (±)-[3H]epinephrine binding was not detectable in calf cortex and rat heart, where (-)-[3H]dihydroalprenolol binding suggests a β1-receptor. A physiological significance of (±)-[3H]epinephrine binding is suggested by the strong correlation for agonists and antagonists between affinities in inhibiting binding, and in stimulating or inhibiting a β-receptor-coupled adenylate cyclase in frog erythrocytes.

Original languageEnglish (US)
Pages (from-to)5090-5102
Number of pages13
JournalJournal of Biological Chemistry
Volume253
Issue number14
StatePublished - Jan 1 1978

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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