"Functional antagonism" is often used to describe the general relaxant effect of beta 2 agonists and
xanthines and their ability to protect the airways against bronchoconstrictor stimuli. This study in guinea pig isolated trachea addresses the question of whether the capacity of these drugs to protect against constrictor stimuli is related to smooth muscle relaxation. Three
antimuscarinic drugs were also examined to determine whether antagonism of mediators other than
muscarinic agonists might contribute to bronchodilatation by these
antimuscarinic drugs.
Terbutaline (1.1 x 10(-7), 2.2 x 10(-7) M),
theophylline (2.2 x 10(-4), 4.4 x 10(-4) M), and
enprofylline (5.2 x 10(-5), 1.0 x 10(-4) M) relaxed the tracheal tension that remained after
indomethacin treatment. They did not, however, alter the
carbachol concentration-response curve significantly. In addition, neither
theophylline (2.2 x 10(-4) M) nor
terbutaline (1.1 x 10(-7) M) altered
histamine induced contraction.
Atropine sulphate,
glycopyrrolate, and
ipratropium bromide had EC50 values of 10(-9) - 10(-8) M for relaxation of
carbachol induced contractions, whereas concentrations of 10(-6) - 10(-3) M or greater were required to relax contractions induced by
allergen and nine other non-
muscarinic mediators. It is suggested that bronchodilatation by
antimuscarinic drugs in vivo is due to inhibition of
acetylcholine induced bronchoconstriction alone and that beta 2 agonists and
xanthines have poor ability to protect airway smooth muscle against constrictor stimuli. Hence mechanisms other than bronchodilatation and "functional antagonism" should be considered to explain the protection against constrictor stimuli in
asthma seen with beta 2 agonists and
xanthines.