Isoproterenol antagonism of cardioselective beta adrenergic receptor blocking agents: a comparative study of human and guinea-pig cardiac and bronchial beta adrenergic receptors.
pA2 values against isoproterenol were determined for a number of cardioselective and noncardioselective beta adrenergic receptor blocking agents using human and guinea-pig isolated atrial and bronchial or tracheal preparations to study possible species differences. No significant differences in pA2 values for propranolol, pindolol, Ro 3-4787, acebutolol, atenolol, practolol, metoprolol, H 87/07 and tolamolol on bronchial or tracheal beta adrenergic receptors of both species were found. With respect to atrial beta adrenergic receptors, significantly lower pA2 values for human preparations, as compared to guinea-pig preparations, were found for tolamolol and CI 775. These are the only two agents in the series that derive their cardioselectivities from specific nitrogen substitutents. The different potencies of only these two compounds in antagonizing isoproterenol on atrial beta adrenergic receptors of both species suggest a difference in an accessory receptor area close to the site that interacts with the nitrogen atom of beta adrenergic agents.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000648:ultrastructure; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000037:antagonists & inhibitors*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000648:ultrastructure; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D013045:Species Specificity; D014132:Trachea / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol