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.

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