Are the pA2 values of selective beta-adrenoceptor antagonists valid when obtained on guinea-pig tracheal preparations contracted with carbachol?

On carbachol-contracted tracheal preparations from guinea-pigs, the slope of the Schild plot for propranolol (isoprenaline as agonist) was 1.0. The slope of the plots for atenolol (beta 1-selective) and butoxamine (beta 2-selective) were less than 1.0, whether isoprenaline or fenoterol was agonist. This was in contrast to previous reports on intrinsic tone tracheal preparations. It was established that the low slopes for atenolol and butoxamine on carbachol-contracted preparations were not related to aspects of the experimental procedures. Low slopes on carbachol-contracted preparations tended to occur when the antagonist used was selective and, although the reason for this is not clear, it may be related to the presence of both beta 1- and beta 2-adrenoceptors in this tissue. Therefore, it is suggested that pA2 values obtained for selective beta-adrenoceptor antagonists on guinea-pig tracheal preparations contracted with carbachol may not be strictly valid, and that antagonists should be studied on intrinsic tone tracheal preparations when pA2 values are to be compared with pA2 values from other tissues to quantify the selectivity of the antagonist.