Abstract
Extracellular purines have a role in renal physiology and adaption to inflammation. However, inflammatory renal disease may be mediated by extracellular purines, resulting in renal injury. The role of purinergic signaling is dependent on the concentrations of extracellular purines. Low basal levels of purines are important in normal homeostasis and growth. Concentrations of extracellular purines are significantly elevated during inflammation and mediate either an adaptive role or propagate local inflammation. Adenosine signaling mediates alterations in regional renal blood flow by regulation of the renal microcirculation, tubulo-glomerular feedback, and tubular transport of sodium and water. Increased extracellular ATP and renal P2 receptor-mediated inflammation are associated with various renal diseases, including hypertension, diabetic nephropathy, and glomerulonephritis. Experimental data suggests P2 receptor deficiency or receptor antagonism is associated with amelioration of antibody-mediated nephritis, suggesting a pathogenic (rather than adaptive) role of purinergic signaling. We discuss the role of extracellular nucleotides in adaptation to ischemic renal injury and in the pathogenesis of inflammatory renal disease.
Highlights
Purines are ubiquitous molecules that are synthesized as nucleosides
Among the endogenous purinergic compounds, adenosine and adenosine -triphosphate (ATP) play a key role in the host response to inflammation via extracellular signaling pathways
The relative contribution of different cell types to the basal levels of extracellular nucleotides and the mechanism of purine release is an area of active research
Summary
University of Pittsburgh School of Medicine, USA. Reviewed by: Shaohu Sheng, University of Pittsburgh, USA Pablo D. Extracellular purines have a role in renal physiology and adaption to inflammation. Inflammatory renal disease may be mediated by extracellular purines, resulting in renal injury. The role of purinergic signaling is dependent on the concentrations of extracellular purines. Concentrations of extracellular purines are significantly elevated during inflammation and mediate either an adaptive role or propagate local inflammation. Increased extracellular ATP and renal P2 receptor-mediated inflammation are associated with various renal diseases, including hypertension, diabetic nephropathy, and glomerulonephritis. Experimental data suggests P2 receptor deficiency or receptor antagonism is associated with amelioration of antibody-mediated nephritis, suggesting a pathogenic (rather than adaptive) role of purinergic signaling. We discuss the role of extracellular nucleotides in adaptation to ischemic renal injury and in the pathogenesis of inflammatory renal disease
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