In vitro Comparison of the Intrinsic Activity of Functional Antagonism between β-agonists and Spasmogens in the Guinea-pig Tracheal Muscle

Abstract

Background: The bronchodilating action of β-agonists depends on the tone of airway smooth muscle or on spasmogen. To estimate the precise intrinsic activity of β-agonists, relaxation responses should be examined on maximally contracted airway smooth muscle. The aim of this study was to compare the relaxation responses to β-agonists under different tonic conditions of airway smooth muscle. Methods: We examined the relaxation response to β-agonists on the isolated tracheal ring preparations in guinea-pigs precontracted with different concentrations of carbachol, leukotriene D4 or substance P, and compared these results with that of spontaneously developed muscle tone. Results: Relaxation responses to β-agonists were diminished depending on the extent of carbachol-induced tone in the tracheal muscle. The degree of hyporesponsiveness was greatest in treatment with tulobuterol, procaterol and isoproterenol, but least with adrenaline, formoterol and salmeterol. Diminished relaxation responses to β-agonists were partially reversed by pretreatment with AF-DX 116, a muscarinic M2 receptor antagonist. When the tracheal muscle was precontracted with different concentrations of leukotriene D4 (1–100 nM) or substance P (0.1-10 μM), a diminished relaxation response to procaterol was not observed. Conclusions: All β-agonists tested were partial agonists for relaxation of the carbachol-contracted guinea-pig tracheal muscle, where adrenaline rather than isoproterenol had the highest intrinsic activity.

Keywords

• carbachol
• contraction
• functional antagonism
• guinea-pig trachea
• intrinsic activity
• potency
• β-agonists