Influence of β1-adrenoceptor blockade on the gene expression of adenylate cyclase subtypes and β-adrenoceptor kinase in human atrium

There is accumulating evidence of cross-regulation between stimulatory G-protein (G_s)-coupled receptors in human atrium. Chronic β₁-adrenoceptor antagonist treatment can sensitize β₂-adrenoreceptors, 5-HT₄ receptors, histamine H₂ receptors and possibly β₄-adrenoreceptors. To investigate the mechanism of such cross-talk between G_s-coupled receptors, we have measured the mRNA expression of the cardiac adenylate cyclases (types IV, V, VI and VII) and of β-adrenoceptor kinase 1 in human atria using TaqMan quantitative PCR, and compared expression between patients chronically receiving a β₁-adrenoceptor antagonist and non-treated patients. The results showed no difference in gene expression between the two groups of patients; however, significant positive correlations of gene expression between adenylate cyclase subtypes were found. We conclude that β₁-adrenoceptor antagonists do not change the absolute levels of gene expression of adenylate cyclase subtypes in human atrium. The co-ordinate regulation among adenylate cyclase subtypes and the influence of β₁-adrenoceptor antagonists need to be investigated further.