Quantification of beta-adrenoceptors and beta-adrenoceptor kinase on protein and mRNA levels in heart failure.
The alterations of the beta-adrenoceptor adenylyl cyclase are reviewed. In failing myocardium, the down-regulation of beta 1-adrenoceptors is accompanied by a decrease in steady state mRNA levels, as studied with quantitative polymerase chain reactions in dilated and ischaemic cardiomyopathy. The density of beta 2-adrenoceptors and beta 2-adrenoceptor mRNA was unchanged in both pathological conditions compared to non-failing myocardium. In addition to down-regulation of beta 1-receptor protein and mRNA, an increased activity of the beta-adrenoceptor kinase (beta-ARK) was observed. Correspondingly, quantification of beta-ARK mRNA by a 5' and a middle portion PCR-product suggests that increased enzyme activity could be due to increased transcription. In summary, decreased steady state levels of beta 1-adrenoceptor mRNA could contribute to reduced beta-adrenoceptor density in failing myocardium. The known uncoupling of beta-adrenoceptors could be due to an increased mRNA expression and activity of beta-ARK.
Böhm
M
M
Klinik III für Innere Medizin, Universität zu Köln, Germany.
Lohse
M J
MJ
D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006333:Heart Failure / Q000235:genetics*; D006801:Humans; D009206:Myocardium / Q000201:enzymology; D009638:Norepinephrine / Q000502:physiology; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D011943:Receptors, Adrenergic, beta / Q000235:genetics*; D014158:Transcription, Genetic; D051552:beta-Adrenergic Receptor Kinases
D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D017868:Cyclic AMP-Dependent Protein Kinases; D051552:beta-Adrenergic Receptor Kinases; D009638:Norepinephrine