Cyclic Adenosine Monophosphate in Cardiac and Sympathoadrenal GLP-1 Receptor Signaling: Focus on Anti-Inflammatory Effects.
Anastasios LymperopoulosJordana I BorgesRenee A StoicovyPublished in: Pharmaceutics (2024)
Glucagon-like peptide-1 (GLP-1) is a multifunctional incretin hormone with various physiological effects beyond its well-characterized effect of stimulating glucose-dependent insulin secretion in the pancreas. An emerging role for GLP-1 and its receptor, GLP-1R, in brain neuroprotection and in the suppression of inflammation, has been documented in recent years. GLP-1R is a G protein-coupled receptor (GPCR) that couples to Gs proteins that stimulate the production of the second messenger cyclic 3',5'-adenosine monophosphate (cAMP). cAMP, acting through its two main effectors, protein kinase A (PKA) and exchange protein directly activated by cAMP (Epac), exerts several anti-inflammatory (and some pro-inflammatory) effects in cells, depending on the cell type. The present review discusses the cAMP-dependent molecular signaling pathways elicited by the GLP-1R in cardiomyocytes, cardiac fibroblasts, central neurons, and even in adrenal chromaffin cells, with a particular focus on those that lead to anti-inflammatory effects by the GLP-1R. Fully elucidating the role cAMP plays in GLP-1R's anti-inflammatory properties can lead to new and more precise targets for drug development and/or provide the foundation for novel therapeutic combinations of the GLP-1R agonist medications currently on the market with other classes of drugs for additive anti-inflammatory effect.
Keyphrases
- protein kinase
- anti inflammatory
- binding protein
- induced apoptosis
- signaling pathway
- drug delivery
- left ventricular
- oxidative stress
- spinal cord
- epithelial mesenchymal transition
- spinal cord injury
- metabolic syndrome
- heart failure
- multiple sclerosis
- small molecule
- cell death
- cell proliferation
- insulin resistance
- blood glucose
- blood brain barrier
- atrial fibrillation
- single molecule
- functional connectivity
- pi k akt