Role of phosphoinositide metabolism in functional antagonism of airway smooth muscle contraction by beta-adrenoceptor agonists

Eur J Pharmacol. 1989 May 11;172(2):175-83. doi: 10.1016/0922-4106(89)90008-4.


Histamine and the muscarinic agonists, methacholine, oxotremorine, and McN-A-343, were used to contract guinea-pig tracheal smooth muscle preparations. Cumulative dose-relaxation curves with isoprenaline were performed subsequently. In addition, the concentration-dependent induction of phosphoinositide metabolism by the contractile agonists was measured in bovine tracheal smooth muscle. All agonists were found to induce a decrease of the apparent affinity of isoprenaline and a loss of relaxation, depending on the concentration and type of contractile agonist used. The differential effects of the contractile agonists, especially at higher and supramaximal concentrations, on these beta-adrenergic parameters could be explained by differences in phosphoinositide metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • (4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride / pharmacology
  • Adrenergic beta-Agonists / pharmacology*
  • Animals
  • Cattle
  • Female
  • Guinea Pigs
  • Histamine / pharmacology
  • In Vitro Techniques
  • Isoproterenol / pharmacology
  • Male
  • Methacholine Compounds / pharmacology
  • Muscle Contraction / drug effects
  • Muscle Relaxation / drug effects
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / metabolism
  • Oxotremorine / pharmacology
  • Phosphatidylinositols / metabolism*
  • Respiratory System / drug effects
  • Trachea / drug effects
  • Trachea / metabolism


  • Adrenergic beta-Agonists
  • Methacholine Compounds
  • Phosphatidylinositols
  • (4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride
  • Oxotremorine
  • Histamine
  • Isoproterenol