Modulation of airway smooth muscle beta-adrenoceptor function by a muscarinic agonist

Life Sci. 1994;54(3):185-91. doi: 10.1016/0024-3205(94)00587-7.


We have investigated the effect of a muscarinic agonist and protein kinase C (PKC) activation on beta-adrenoceptors and their coupling to adenylyl cyclase in bovine tracheal smooth muscle. There was a significant reduction in maximum binding capacity of [125I]iodocyanopindolol ([125I]ICYP) after exposure to carbachol and 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA). Similarly both carbachol and PMA inhibited the 5'-guanylylimidodiphosphate-induced shift in [125I]ICYP binding by isoproterenol and significantly decreased isoproterenol-induced cyclic AMP accumulation. A phorbol ester, 4 alpha-phorbol 12,13-didecanoate which does not activate PKC had no effect on beta-receptor binding or coupling. These results suggest that PKC activation directly via a phorbol ester and indirectly via muscarinic receptor stimulation may lead to reduction and uncoupling of beta-receptors in airway smooth muscle. We suggest that this mechanism may be relevant to the reduction in beta-receptor coupling in asthmatic airways as an effect of PKC activation by inflammatory mediators and neurotransmitters.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Agonists / pharmacology
  • Animals
  • Binding, Competitive
  • Carbachol / pharmacology*
  • Cattle
  • Cyclic AMP / metabolism
  • Enzyme Activation
  • GTP-Binding Proteins / metabolism
  • Isoproterenol / metabolism
  • Isoproterenol / pharmacology
  • Kinetics
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / metabolism*
  • Muscle, Smooth / ultrastructure*
  • Protein Kinase C / metabolism
  • Radioligand Assay
  • Receptors, Adrenergic, beta / drug effects*
  • Receptors, Adrenergic, beta / metabolism*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Trachea / drug effects
  • Trachea / metabolism*
  • Trachea / ultrastructure*


  • Adrenergic beta-Agonists
  • Receptors, Adrenergic, beta
  • Carbachol
  • Cyclic AMP
  • Protein Kinase C
  • GTP-Binding Proteins
  • Isoproterenol
  • Tetradecanoylphorbol Acetate