β-Adrenoceptor desensitization despite cardiac denervation in human failing transplanted myocardium

The aim of this study, using right ventricular endomyocardial biopsies, was to determine whether adenylyl cyclase activity is decreased — despite cardiac denervation — in human failing transplanted myocardium. β-Adrenoceptor-stimulated adenylyl cyclase activity in membranes of moderately failing transplanted hearts was significantly decreased by 49% in comparison to non-failing transplanted hearts. Receptor-independent adenylyl cyclase stimulation (forskolin + GTP, forskolin + Mn2+) and the level of inhibitory G protein α-subunits were not significantly different in membranes of failing vs. non-failing transplanted myocardium. The results indicate that similar to failing non-transplanted myocardium the responsiveness to β-adrenoceptor agonists is also decreased in failing transplanted myocardium.