The effect of the beta-adrenoreceptor antagonist Ro03-7894 on rat atrial tension development and (-)-[3H]dihydroalprenolol binding to cardiac and lung membranes.
The ability of 1-(5-chloracetylaminobenzfuran-2-yl)-2-isopropylaminoethanol (Ro03-7894) to irreversibly inactivate beta-adrenoreceptors was studied. In isolated rat atria Ro03-7894 (500 microM) depressed and shifted the tension development curve for isoproterenol to the right. After a 2 hour washout period the dose response curve for isoproterenol was further depressed. At a lower dose of Ro03-7894 (50 microM), the isoproterenol dose response curve was also depressed and shifted to the right although after a 2 hour washout, the sensitivity to isoproterenol was restored but the maximum response was still depressed. Ro03-7894 (50 microM) also depressed the tension development response to increasing concentrations of external calcium. The concentration of Ro03-7894 that inhibited (-)-[3H]dihydroalprenolol (DHA) binding by 50% in cardiac and lung membranes was 20 microM. Incubation of rat ventricular or lung membranes for 1 hour with 100 microM Ro03-7894 followed by washing did not change the concentration of beta-adrenoreceptors or the KD values for [3H]DHA binding. Furthermore, neither the concentration of beta-adrenoreceptors nor the KD for [3H]DHA binding was changed in cardiac and lung membranes at 4 or 24 hours after an i.p. injection of 20 mg/kg of Ro03-7894. The results suggested that Ro03-7894 was a relatively weak beta-adrenoreceptor antagonist which under the conditions used did not irreversibly inactivate the receptor but probably depressed tension development in intact atria nonspecifically.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000526:Alprenolol / Q000031:analogs & derivatives*; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism; D004082:Dihydroalprenolol / Q000378:metabolism*; D007545:Isoproterenol / Q000037:antagonists & inhibitors; D007700:Kinetics; D008168:Lung / Q000378:metabolism*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D051381:Rats
D000319:Adrenergic beta-Antagonists; D001572:Benzofurans; D004082:Dihydroalprenolol; C018430:Ro 03-7894; D000526:Alprenolol; D007545:Isoproterenol