Related Experiment Videos

Adenosine receptors and second messenger signaling pathways in rat cardiac fibroblasts

Sara A Epperson1, Laurence L Brunton, Israel Ramirez-Sanchez

  • 1Department of Medicine, University of California, La Jolla, CA, USA.

American Journal of Physiology. Cell Physiology
|February 27, 2009
PubMed

Insights

Adenosine (ADO) may help heart failure by inhibiting cardiac fibroblast proliferation. This study identified adenosine receptors (ARs) and found that A(2a) and A(2b) receptors mediate ADO signaling via cAMP, impacting cell behavior.

Area of Science:

  • Cardiovascular Biology
  • Cellular Signaling
  • Pharmacology

Background:

  • Adenosine (ADO) inhibits cardiac fibroblast (CF) proliferation and collagen synthesis, potentially mitigating adverse cardiac remodeling in heart failure.
  • The specific signaling pathways modulated by ADO in CF to alter cell phenotype remain largely unknown.

Purpose of the Study:

  • To identify adenosine receptors (ARs) and their associated signaling pathways in primary cultures of adult rat cardiac fibroblasts (CF).
  • To elucidate the mechanisms by which ADO influences CF phenotype and function.

Main Methods:

  • Quantitative RT-PCR was used to detect the expression of all four known AR subtypes (A(1)R, A(2a)R, A(2b)R, A(3)R) in rat CF.
  • Subtype-specific agents and pertussis toxin were employed to investigate AR coupling to G proteins (G(q), G(s), G(i)) and downstream signaling pathways, including calcium mobilization and adenylyl cyclase activity.
  • Extracellular signal-regulated kinase 1/2 (ERK1/2) activity was measured in response to agents that elevate cyclic adenosine monophosphate (cAMP).

Main Results:

  • All four AR subtypes (A(1)R, A(2a)R, A(2b)R, A(3)R) were detected in rat CF, with A(2) receptor subtypes being more prevalent.
  • Adenosine receptors did not show coupling to the G(q)-phospholipase C pathway or calcium mobilization.
  • A(2a)R and A(2b)R were found to couple to G(s)-adenylyl cyclase, while A(1)R showed weak coupling to G(i)-adenylyl cyclase. Elevated cAMP stimulated ERK1/2 activity in a pertussis toxin-insensitive manner.

Conclusions:

  • Adenosine signaling in adult rat cardiac fibroblasts primarily involves A(2a) and A(2b) receptors.
  • These receptors likely mediate their effects through cAMP-dependent signaling pathways.
  • The identified signaling cascade, involving cAMP and ERK1/2 activation, is crucial for understanding ADO's role in regulating CF phenotype and potential therapeutic applications in heart failure.

Related Concept Videos

What are Second Messengers?01:12

What are Second Messengers?

Because many receptor binding ligands are hydrophilic, they do not cross the cell membrane and thus their message must be relayed to a second messenger on the inside. There are several second messenger pathways, each with their own way of relaying information. G-protein coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol path is active when the receptor induces phospholipase C to hydrolyze the phospholipid,...
90.7K
Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
3.2K
Amplifying Signals via Second Messengers01:15

Amplifying Signals via Second Messengers

Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
8.7K
Intracellular Signaling Cascades01:24

Intracellular Signaling Cascades

Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
53.5K
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
6.6K
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
10.1K