Article

Adenosine A(2B) receptor mediates an increase on VEGF-A production in rat kidney glomeruli.

Laboratorio de Patología Molecular (LPM), Instituto de Bioquímica, Facultad de Ciencias, Universidad Austral de Chile, P.O. Box 567, Campus Isla Teja, Valdivia, Chile.
Biochemical and Biophysical Research Communications (impact factor: 2.48). 03/2008; 366(1):180-5. DOI:10.1016/j.bbrc.2007.11.113 pp.180-5
Source: PubMed

ABSTRACT Up-regulation of the glomerular expression and the activity of vascular endothelial growth factor-A (VEGF) have been identified as an early pathogenic event for the progression of diabetic nephropathy. Currently, however the mediators are not yet clearly recognized. In this study we identified all four adenosine receptor (AR) subtypes, i.e. A(1), A(2A), A(2B) and A(3) in isolated rat kidney glomeruli. We localized the expression of A(2B)AR in podocytes, the primary VEGF producing cells. The ex vivo treatment of kidney glomeruli with adenosine or a general AR agonist NECA, increases VEGF protein content. In addition, NECA treatment elicits VEGF release. These effects were blocked by the A(2B)AR selective antagonist MRS1754 supplementation. Furthermore, we showed that A(2B)AR activation was necessary to promote a higher expression of VEGF in kidney glomeruli upon exposure to high d-glucose concentration, a pathogenic condition like those observed in diabetic nephropathy.

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    Article: Do adenosine receptors offer new therapeutic options for diabetic nephropathy?
    Rody San Martín, Denisse Valladares, Horacio Roa, Evelin Troncoso, Luis Sobrevia
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    ABSTRACT: Diabetes mellitus is currently considered to be an epidemic disease. Approximately a third of individuals with type 1 and type 2 diabetes develop persistent albuminuria, lose renal function, and are at increased risk of cardiovascular and other microvascular complications. Diabetic nephropathy (DN) is the primary cause of end stage renal disease throughout the world. Microvascular dysfunction in the glomerulus appears as an early pathogenic event in progression of this renal complication. In recent years, studies with animal knockout (KO) models have revealed that uncoupling of the vascular endothelial growth factor/nitric oxide (VEGF/NO) axis leads to the glomerular alterations that characterize diabetic nephropathy. Therefore, new therapeutic alternatives may usefully target VEGF overproduction or endothelial nitric oxide availability. Recent studies also demonstrate a role for adenosine receptors in glomerular physiology and VEGF production that looks promising for therapeutic intervention of the evolution of diabetic nephropathy. However further progress is required in order to understand the dynamics of local adenosine production, in particular the extracellular metabolism of adenine nucleotides by ectoenzymes and the role of nucleoside transporters on external adenosine accumulation in the glomerulus in the pathological state. So far there is no assay that is sufficiently sensitive and accurate for subclinical diagnoses of this renal disease, which is complicated and costly to patients with often devastating effects. Current studies using proteomics offer promising alternatives for the identification of new renal injury markers. It is hoped these will permit evaluation of new therapeutic tools for more opportune intervention of this disease.
    Current Vascular Pharmacology 11/2009; 7(4):450-9. · 2.90 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

A(2B)AR selective antagonist MRS1754 supplementation
 
d-glucose concentration
 
ex vivo treatment
 
four adenosine receptor
 
general AR agonist NECA
 
glomerular expression
 
higher expression
 
increases VEGF protein content
 
kidney glomeruli
 
NECA treatment elicits VEGF release
 
pathogenic condition
 
pathogenic event
 
primary VEGF
 
progression
 
rat kidney glomeruli