Ligand modulation of [35S]GTPgammaS binding at human alpha(2A), alpha(2B) and alpha(2C) adrenoceptors

Cell Signal. 2002 Oct;14(10):829-37. doi: 10.1016/s0898-6568(02)00030-x.


Affinities and efficacies of chemically diverse ligands--some of them used as clinical agents--were examined, employing [3H]RX821,002 and [35S]GTPgammaS binding assays, respectively, at human (h) cloned, halpha(2A), halpha(2B) and halpha(2C) adrenoceptors (AR) expressed in Chinese hamster ovary (CHO) cells. As compared to noradrenaline (NA, efficacy defined as 100%), the majority of the 13 agonists tested generally behaved as partial agonists. Amongst 18 antagonists, pK(B) and pK(i) values, which were highly correlated for each alpha(2)-AR subtype, failed to reveal any strikingly selective agents. Inverse agonist properties were not detected for any antagonist, consistent with a lack of constitutive activity suggested by the monophasic inhibition of [35S]GTPgammaS binding by GTPgammaS. These data should facilitate interpretation of experimental and clinical actions of adrenergic agonists. Moreover, they emphasize the continuing need for alpha(2)-AR subtype-selective antagonists in order to define further the roles and therapeutic relevance of halpha(2A)-, halpha(2B)-, and halpha(2C)-AR.

Publication types

  • Comparative Study

MeSH terms

  • Adrenergic alpha-Agonists / pharmacology*
  • Adrenergic alpha-Antagonists / pharmacology*
  • Animals
  • Binding Sites / drug effects
  • Binding Sites / physiology
  • Binding, Competitive / drug effects
  • Binding, Competitive / physiology
  • CHO Cells / drug effects
  • CHO Cells / metabolism*
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cricetinae
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Humans
  • Norepinephrine / metabolism
  • Norepinephrine / pharmacology
  • Receptors, Adrenergic, alpha-2 / drug effects
  • Receptors, Adrenergic, alpha-2 / genetics
  • Receptors, Adrenergic, alpha-2 / metabolism*
  • Sodium Chloride / pharmacology
  • Sulfur Radioisotopes
  • Transfection


  • ADRA2A protein, human
  • ADRA2B protein, human
  • ADRA2C protein, human
  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • Receptors, Adrenergic, alpha-2
  • Sulfur Radioisotopes
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Sodium Chloride
  • Norepinephrine