Overexpression of β1‐adrenoceptors in adult rat ventricular myocytes enhances CGP 12177A cardiostimulation: implications for ‘putative’β4‐adrenoceptor pharmacology

摘要: 1. CGP 12177A mediates cardiostimulation by activation of the 'putative' beta(4)-adrenoceptor; however, it has recently been reported that disruption beta(1)-adrenoceptor gene abolishes this effect. We have adenovirally overexpressed beta(1)-adrenoceptors in isolated, cultured adult rat ventricular cardiomyocytes and observed inotropic potency isoprenaline (in presence 1 microm propranolol). 2. Isoprenaline was a full agonist at myocytes (pD(2) 7.69+/-0.12). nonconventional partial 6.34+/-0.09), increasing inotropy lusitropy, with an intrinsic activity 0.34 antagonised bupranolol. 3. overexpression enhanced 11.7-fold 8.76+/-0.14) 5.9-fold (7.11+/-0.10), respectively. Green fluorescent protein (GFP) did not alter or 7.41+/-0.24 pD(2) 6.60+/-0.50, respectively). 4. The cardiostimulant effects were IBMX (phosphodiesterase inhibitor) decreased Rp-cAMPS (cAMP antagonist). also increased cAMP levels. but initiated arrhythmias lower concentrations following overexpression. 5. (125)I-Cyanopindolol saturation binding Adv.beta(1) demonstrated approximately 18-fold increase beta(1)-adrenoceptors. (3)H-CGP binding, propranolol, 5-fold 6. This study demonstrates propranolol) overexpressing beta(1)-adrenoceptors, mediated Gs/cAMP signalling pathway. 'Putative' beta(4)-adrenoceptor pharmacology appears to be novel affinity state beta(1)-adrenoceptor.