The importance of choice of agonist in studies designed to predict ? 2:? 1 adrenoceptor selectivity of antagonists from pA2 values on guinea-pig trachea and atria

Abstract

PA₂ values have been obtained for propranolol, butoxamine, H35/25 and atenolol on guinea-pig isolated trachea and atria (rate) using noradrenaline (β ₁-selective), isoprenaline (non-selective) and fenoterol (β ₂-selective) as agonists. pA₂ values varied with the agonist used on trachea but not on atria and, therefore, trachea: atria selectivity values varied with the agonist used. It is suggested that the best estimate of the selectivity of an antagonist between β ₂- and β ₁-adrenoceptors is obtained by comparing its pA₂ value obtained on trachea using a β ₂-selective agonist with that obtained on atria using a β ₁-selective agonist. The reasons for this are discussed. The quantitative values for β ₂:β ₁ selectivity obtained using the above pA₂ values were butoxamine 17.0, H35/25 13.5, propranolol 2.75 and atenolol 0.036, i.e. butoxamine and H35/25 were β ₂-selective, propranolol was non-selective and atenolol was β ₁-selective. The results support the hypotheses that guinea-pig trachea contains a mixture of β ₁- and β ₂-adrenoceptors and that guinea-pig atria contain only β ₁-adrenoceptors.