THE SELECTIVE ACTION OF /B-ADRENOCEPTOR BLOCKING DRUGS AND THE NATURE OF /3l and /2 ADRENOCEPTORS

1 Purified membranes retaining a catecholamine responsive adenylate cyclase have been prepared from rabbit heart, lung and (pseudo-pregnant) uterus. 2 These preparations have the characteristics of plasma membranes and both heart and lung respond to P-adrenoceptor agonists in the order: (± )-isoprenaline > (-)-noradrenaline > (-)-adrenaline > ( + )-isoprenaline > salbutamol. The sensitivity of the adenylate cyclase to,-adrenoceptor stimulation is improved by pre-treatment of the animals with reserpine and syrosingopine. 3 Dose-ratios for several concentrations of propranolol (non-selective /-adrenoceptor blocker), practolol and atenolol (cardio-selective /i-adrenoceptor blockers) have been measured on all three membrane preparations. Schild plots of log (dose ratio -1) vs. log dose were virtually coincident for heart and lung with a dissociation constant (Kb) for propranolol very close to the pharmacological value. The ratio of Kb values was 0.65 for practolol and 1.23 for atenolol compared with pharmacological cardio-selectivity ratios (measured on isolated atria and tracheal chain) of 67.6 and