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.