标题：Increased expression of adenylylcyclase type VI proportionately increases β-adrenergic receptor-stimulated production of cAMP in neonatal rat cardiac myocytes
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1998
卷号：95
期号：3
页码：1038-1043
DOI：10.1073/pnas.95.3.1038
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Cellular content of cAMP generated by activation of adenylylcyclase (AC; EC 4.6.1.1) is a key determinant of functional responsiveness in the heart and other tissues. We have tested two hypotheses regarding the relationship between AC content and {beta}-adrenergic receptor ({beta}AR)-mediated signal transduction in cardiac myocytes. First, that AC content limits adrenergic signal transduction, and, second, that increased AC, independent of ({beta}AR) number and G-protein content, yields a proportional increase in {beta}AR-mediated transmembrane signaling. We used recombinant adenovirus to increase AC isoform VI (ACVI) expression in neonatal cardiac myocytes. Cells that overexpressed ACVI responded to agonist stimulation with marked increases in cAMP production in proportion to protein expressed. In parallel experiments performed on cells transfected with lacZ (control) or ACVI, [3H]forskolin binding, used to assess AC protein expression, was amplified 6-fold, while {beta}AR-stimulated cAMP production from these cells was increased 7-fold. No changes in {beta}AR number, or in the heterotrimeric GTP-binding proteins, Gs or Gi2, were observed. Previous studies indicate that increased cardiac expression of {beta}AR or Gs does not yield proportional increases in transmembrane adrenergic signaling. In contrast, the current data demonstrate that increased ACVI expression provides a proportional increase in {beta}-adrenergic signal transduction. Our results show that the amount of AC sets a limit on transmembrane {beta}-adrenergic signaling. We speculate that similar functional responses are possible in other cell types in which AC plays an important physiological role.
