Biochemical and Molecular Characteristics of β-Adrenergic Receptor Binding Sites

  • Lee E. Limbird
  • Robert J. Lefkowitz
Part of the NATO Advanced Study Institutes Series book series (NSSA, volume 11)


The availability of radiolabeled hormones, drugs and analogs which retain their characteristic biological activity and selectivity has provided a valuable tool for the study of the interaction of these agents with their target cell receptors. Despite the major advances in the investigation of receptors for polypeptide (14, 37) and steroid hormones (13) and nicotinic cholinergic drugs (11) using these techniques, the confident identification of the β-adrenergic receptors for catecholamines has remained until recently an elusive goal. Initial studies employed tritium labeled β-adrenergic agonists to identify binding sites in membrane fractions containing catecholamine-sensitive adenylate cyclase. However, some of the characteristics of binding observed with these agents diverged from which might be expected of the physiological β-adrenergic receptor (3, 17, 18). Perhaps the difficulties in these studies can be attributed to: 1) the multiple potential binding sites in addition to the adenylate cyclase coupled β-adrenergic receptor for labeled native catecholamines, 2) the relatively low affinity for cata-cholamines in in vitro membrane preparations (KD ≅ 10−6M), 3) the unimpressive specific radioactivity of available tritiated ligands (≅ 1 Ci/mmol), or 4) the absence of tissue preparations which provided a high concentration of β-adrenergic receptors relative to other constituents. Even in the case of the high affinity β-adrenergic antagonist propranolol, which would not likely interact with degradative enzymes and uptake mechanisms directed at catecholamines, binding characteristics indicated that this ligand binds disproportionately to non β-adrenergic receptor sites (40), possibly those responsible for the so-called “anaesthetic” properties of this drug.


Adenylate Cyclase Membrane Preparation Negative Cooperativity Adenylate Cyclase System Confident Identification 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Plenum Press, New York 1976

Authors and Affiliations

  • Lee E. Limbird
    • 1
  • Robert J. Lefkowitz
    • 1
  1. 1.Department of MedicineDuke University Medical CenterDurhamUSA

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