RGD Reference Report - Angiotensin II enhances adenylyl cyclase signaling via Ca2+/calmodulin. Gq-Gs cross-talk regulates collagen production in cardiac fibroblasts. - Rat Genome Database

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Angiotensin II enhances adenylyl cyclase signaling via Ca2+/calmodulin. Gq-Gs cross-talk regulates collagen production in cardiac fibroblasts.

Authors: Ostrom, RS  Naugle, JE  Hase, M  Gregorian, C  Swaney, JS  Insel, PA  Brunton, LL  Meszaros, JG 
Citation: Ostrom RS, etal., J Biol Chem. 2003 Jul 4;278(27):24461-8. Epub 2003 Apr 23.
RGD ID: 2312674
Pubmed: (View Article at PubMed) PMID:12711600
DOI: Full-text: DOI:10.1074/jbc.M212659200

Cardiac fibroblasts regulate formation of extracellular matrix in the heart, playing key roles in cardiac remodeling and hypertrophy. In this study, we sought to characterize cross-talk between Gq and Gs signaling pathways and its impact on modulating collagen synthesis by cardiac fibroblasts. Angiotensin II (ANG II) activates cell proliferation and collagen synthesis but also potentiates cyclic AMP (cAMP) production stimulated by beta-adrenergic receptors (beta-AR). The potentiation of beta-AR-stimulated cAMP production by ANG II is reduced by phospholipase C inhibition and enhanced by overexpression of Gq. Ionomycin and thapsigargin increased intracellular Ca2+ levels and potentiated isoproterenol- and forskolin-stimulated cAMP production, whereas chelation of Ca2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N', N'-tetraacetic acid/AM inhibited such potentiation. Inhibitors of tyrosine kinases, protein kinase C, or Gbetagamma did not alter this cross-talk. Immunoblot analyses showed prominent expression of adenylyl cyclase 3 (AC3), a Ca2+-activated isoform, along with AC2, AC4, AC5, AC6, and AC7. Of those isoforms, only AC3 and AC5/6 proteins were detected in caveolin-rich fractions. Overexpression of AC6 increased betaAR-stimulated cAMP accumulation but did not alter the size of the ANG II potentiation, suggesting that the cross-talk is AC isoform-specific. Isoproterenol-mediated inhibition of serum-stimulated collagen synthesis increased from 31 to 48% in the presence of ANG II, indicating that betaAR-regulated collagen synthesis increased in the presence of ANG II. These data indicate that ANG II potentiates cAMP formation via Ca2+-dependent activation of AC activity, which in turn attenuates collagen synthesis and demonstrates one functional consequence of cross-talk between Gq and Gs signaling pathways in cardiac fibroblasts.

Annotation

Gene Ontology Annotations    

Biological Process

Cellular Component
membrane  (IDA)

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Adcy2  (adenylate cyclase 2)
Adcy3  (adenylate cyclase 3)
Adcy4  (adenylate cyclase 4)
Adcy5  (adenylate cyclase 5)
Adcy6  (adenylate cyclase 6)
Adcy7  (adenylate cyclase 7)

Objects referenced in this article
Gene Cav1 caveolin 1 Rattus norvegicus

Additional Information