Unknown

Dataset Information

0

Regulation of cardiac fibroblast collagen synthesis by adenosine: roles for Epac and PI3K.


ABSTRACT: Rat cardiac fibroblasts (CF) express multiple adenosine (ADO) receptors. Pharmacological evidence suggests that activation of A(2) receptors may inhibit collagen synthesis via adenylyl cyclase-induced elevation of cellular cAMP. We have characterized the signaling pathways involved in ADO-mediated inhibition of collagen synthesis in primary cultures of adult rat CF. ANG II stimulates collagen production in these cells. Coincubation with agents that elevate cellular cAMP [the ADO agonist, 5'-N-ethylcarboxamidoadensoine (NECA), and forskolin] inhibited the stimulatory effects of ANG II. However, direct stimulators and inhibitors of protein kinase A (PKA) did not alter ANG II-induced collagen synthesis, indicating that PKA does not mediate the inhibitory effects of NECA. Inhibitors of AMP-kinase (AMPK) and extracellular signal-regulated kinase 1/2 (ERK1/2) do not alter NECA-inhibited collagen synthesis. However, activation of exchange factor directly activated by cAMP (Epac) mimicked the effects of NECA on ANG II-stimulated collagen synthesis. Inhibition of phosphoinositol-3 kinase (PI3K) reduced the inhibitory effects of NECA on ANG II-induced collagen synthesis, suggesting that NECA acts via PI3K. Furthermore, inhibition of PI3K also relieved the inhibitory effect of Epac activation on ANG II-stimulated collagen synthesis. Thus it appears that ADO activates the A(2)R-G(s)-adenylyl cyclase pathway and that the resultant cAMP reduces collagen synthesis via a PKA-independent, Epac-dependent pathway that feeds through PI3K.

SUBMITTER: Villarreal F 

PROVIDER: S-EPMC2681376 | BioStudies | 2009-01-01

REPOSITORIES: biostudies

Similar Datasets

2018-01-01 | S-EPMC5940627 | BioStudies
1000-01-01 | S-EPMC4042107 | BioStudies
2013-01-01 | S-EPMC3889389 | BioStudies
2010-01-01 | S-EPMC3100203 | BioStudies
2011-01-01 | S-EPMC4114346 | BioStudies
1000-01-01 | S-EPMC2729034 | BioStudies
2008-01-01 | S-EPMC2215344 | BioStudies
1000-01-01 | S-EPMC1334627 | BioStudies
2006-01-01 | S-EPMC2519952 | BioStudies
2015-01-01 | S-EPMC4504471 | BioStudies