Antagonism with dibenamine, D-600, and Ro 3-7894 to estimate dissociation constants and receptor reserves for cardiac adrenoceptors in isolated rabbit papillary muscles.
In papillary muscles isolated from reserpinized rabbits, positive inotropic responses to the alpha (alpha)-adrenergic agonist, (-)-phenylephrine in the presence of 10(7) M timolol and the beta (beta)-adrenergic agonist. (-)-isoproterenol were antagonized with the irreversible alpha-adrenergic antagonist, dibenamine, the irreversible beta-adrenergic antagonist. Ro 3-7894, and the calcium blocker, D-600. D-600 was employed as a functional antagonist of both alpha- and beta-adrenoceptor responses. Dissociation constants (Ka values) for drug-receptor interactions were calculated by the method of Furchgott and used to estimate fractional receptor occupancy and agonist efficacies. Comparison of responses showed that the receptor reserve for cardiac beta-adrenoceptors was greater than for alpha-adrenoceptors. D-600 was an effective inhibitor of both cardiac alpha- and beta-adrenoceptor responses; however, estimates of KA and receptor reserves were similar to estimates using an irreversible antagonist for alpha-but not beta-adrenoceptors.
D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D003983:Dibenzylchlorethamine / Q000494:pharmacology; D005260:Female; D005711:Gallopamil / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013999:Timolol / Q000494:pharmacology
D001572:Benzofurans; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D010656:Phenylephrine; D005711:Gallopamil; D003983:Dibenzylchlorethamine; C018430:Ro 03-7894; D013999:Timolol; D007545:Isoproterenol