Beta-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. beta-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 alpha-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 beta-adrenoceptor agonists is also decreased in failing transplanted myocardium.
Medizinische Klinik I, Klinikum Grosshadern, Universität München, Germany.
C
C
Reithmann
W
W
von Scheidt
K
K
Werdan
D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D001706:Biopsy; D005576:Colforsin / Q000494:pharmacology; D003714:Denervation / Q000009:adverse effects*; D019204:GTP-Binding Proteins / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000494:pharmacology; D016027:Heart Transplantation / Q000473:pathology / Q000502:physiology*; D006352:Heart Ventricles / Q000294:innervation* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology*; D016277:Ventricular Function, Left
D000318:Adrenergic beta-Agonists; D005576:Colforsin; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D007545:Isoproterenol