Role of phosphoinositide metabolism in functional antagonism of airway smooth muscle contraction by beta-adrenoceptor agonists.
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.
Van Amsterdam
R G
RG
Department of Pharmacology and Therapeutics, University of Groningen, The Netherlands.
Meurs
H
H
Brouwer
F
F
Postema
J B
JB
Timmermans
A
A
Zaagsma
J
J
D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008688:Methacholine Compounds / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D010095:Oxotremorine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D012137:Respiratory System / Q000187:drug effects; D014132:Trachea / Q000187:drug effects / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D008688:Methacholine Compounds; D010716:Phosphatidylinositols; D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride; D010095:Oxotremorine; D006632:Histamine; D007545:Isoproterenol