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.
Wang
T
T
Clinical Pharmacology Unit, Addenbrooke's Centre for Clinical Investigation (ACCI), Box 110, Addenbrooke's Hospital, Hills Road, University of Cambridge, Cambridge CB2 2QQ, U.K. tw10001@cus.cam.ac.uk
Brown
M J
MJ
D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000368:Aged; D001262:Atenolol / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D051552:beta-Adrenergic Receptor Kinases
D000319:Adrenergic beta-Antagonists; D007527:Isoenzymes; D012333:RNA, Messenger; D001262:Atenolol; D017868:Cyclic AMP-Dependent Protein Kinases; D051552:beta-Adrenergic Receptor Kinases; D000262:Adenylyl Cyclases