Human beta 1- and beta 2-adrenergic receptor binding and mediated accumulation of cAMP in transfected Chinese hamster ovary cells. Profile of nebivolol and known beta-adrenergic blockers

Biochem Pharmacol. 1991 Oct 9;42(9):1683-9. doi: 10.1016/0006-2952(91)90502-v.


The interaction of nebivolol and its SRRR and RSSS enantiomers, and of known beta-adrenergic blockers, with human beta 1- and beta 2-adrenergic receptors expressed separately in Chinese hamster ovary cells in culture (CHO-Hu beta 1 and CHO-Hu beta 2), was investigated. We studied [3H]CGP-12177 binding to the intact cells and the accumulation of cAMP induced by isoproterenol. Each of the receptor subtypes displayed saturable [3H]CGP-12177 binding on intact cells with sub-nanomolar affinity. The density of beta 1- and beta 2-adrenergic receptor sites was 1.1 x 10(6) receptor binding sites per CHO-Hu beta 1 cell and 0.2 x 10(6) receptor binding sites per CHO-Hu beta 2 cell, respectively. The beta-adrenergic antagonists CGP 20712-A, ICI 118-551 and propranolol showed the same binding properties as beta-adrenergic receptors in previously described tissues or cells. The potencies of these compounds in inhibiting beta-adrenergic receptor mediated accumulation of cAMP corresponded well with their binding affinities. d-Nebivolol (SRRR) and nebivolol showed combined high affinity and selectivity for inhibition of beta 1-adrenergic receptor coupled accumulation of cAMP in CHO-Hu beta 1 cells (0.41 and 0.42 nM for d-nebivolol and nebivolol, respectively). l-Nebivolol (RSSS) was 1460 times less potent than d-nebivolol in CHO-Hu beta 1 cells. The binding affinities of d-nebivolol and nebivolol for human beta 1-adrenergic binding sites correlated well with their potencies in inhibiting beta 1-adrenergic receptor coupled accumulation of cAMP. CHO cells transfected with human beta 1- and beta 2-adrenergic receptors are a valid model system for studying the interaction of compounds with human beta-adrenergic receptors.

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology*
  • Animals
  • Benzopyrans / pharmacology*
  • Binding Sites
  • Binding, Competitive
  • Cell Line
  • Cricetinae
  • Cricetulus
  • Cyclic AMP / metabolism*
  • Ethanolamines / pharmacology*
  • Humans
  • Imidazoles / pharmacology
  • Isoproterenol / antagonists & inhibitors
  • Isoproterenol / pharmacology
  • Models, Biological
  • Nebivolol
  • Propanolamines / antagonists & inhibitors
  • Propanolamines / pharmacology
  • Propranolol / pharmacology
  • Radioligand Assay
  • Receptors, Adrenergic, beta / drug effects
  • Receptors, Adrenergic, beta / genetics
  • Receptors, Adrenergic, beta / metabolism*
  • Stereoisomerism
  • Transfection


  • Adrenergic beta-Antagonists
  • Benzopyrans
  • Ethanolamines
  • Imidazoles
  • Propanolamines
  • Receptors, Adrenergic, beta
  • Nebivolol
  • ICI 118551
  • Propranolol
  • CGP 20712A
  • Cyclic AMP
  • Isoproterenol
  • CGP 12177