Influence of beta1-adrenoceptor blockade on the gene expression of adenylate cyclase subtypes and beta-adrenoceptor kinase in human atrium.

There is accumulating evidence of cross-regulation between stimulatory G-protein (G(s))-coupled receptors in human atrium. Chronic beta(1)-adrenoceptor antagonist treatment can sensitize beta(2)-adrenoreceptors, 5-HT(4) receptors, histamine H(2) receptors and possibly beta(4)-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 beta-adrenoceptor kinase 1 in human atria using TaqMan quantitative PCR, and compared expression between patients chronically receiving a beta(1)-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 beta(1)-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 beta(1)-adrenoceptor antagonists need to be investigated further.