The importance of choice of agonist in studies designed to predict beta 2 : beta 1 adrenoceptor selectivity of antagonists from pA2 values on guinea-pig trachea and atria.
1. pA2 values have been obtained for propranolol, butoxamine, H35/25 and atenolol on guinea-pig isolated trachea and atria (rate) using noredrenaline (beta 1-selective), isoprenaline (non-selective) and fenoterol (beta 2-selective) as agonists. 2. pA2 values varied with the agonist used on trachea but not on atria and, therefore, trachea : atria selectivity values varied with the agonist used. 3. It is suggested that the best estimate of the selectivity of an antagonist between beta 2- and beta 1-adrenoceptors is obtained by comparing its pA2 value obtained on trachea using a beta 2-selective agonist with that obtained on atria using a beta 1-selective agonist. The reasons for this are discussed. 4. The quantitative values for beta 2 : beta 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 beta 2-selective, propranolol was non-selective and atenolol was beta 1-selective. 5. The results support the hypotheses that guinea-pig trachea contains a mixture of beta 1- and beta 2-adrenoceptors and that guinea-pig atria contain only beta 1-adrenoceptors.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D004347:Drug Interactions; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D014132:Trachea / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta