A_2Aadenosine receptor-mediated inhibition of renal injury and neutrophil adhesion

Abstract

We sought to determine the mechanisms responsible for the reduced renal tissue injury by agonists of A(2A) adenosine receptors (A(2A)-ARs) in models of ischemia-reperfusion (I/R) injury. DWH-146e, a selective A(2A)-AR agonist, was administered subcutaneously to Sprague-Dawley rats and C57BL/6 mice via osmotic minipumps, and animals were subjected to I/R. I/R led to an increase in plasma creatinine and kidney neutrophil infiltration. Infusion of DWH-146e at 10 ng. kg(-1). min(-1) produced a 70% reduction in plasma creatinine as well as a decrease in neutrophil density in outer medulla and cortex and myeloperoxidase activity in the reperfused kidney. Myeloperoxidase activity in kidney correlated with the degree of renal injury. P-selectin and intercellular adhesion molecule 1 (ICAM-1) immunoreactivity were most prominent in endothelial cells of peritubular capillaries and interlobular arteries of cortex and outer and inner medulla of vehicle-treated mice whose kidneys were subjected to I/R. DWH-146e treatment led to a pronounced decrease in P-selectin- and ICAM-1-like immunoreactivity. These data are consistent with our hypothesis that A(2A)-AR agonists limit I/R injury due to an inhibitory effect on neutrophil adhesion.

Early Renal Injury Induced by Caffeine Consumption in Obese, Diabetic ZSF1Rats

“…[27,28] Through the activation of the A2B receptor, adenosine inhibits macrophages proliferation [29] and reduces the activity of NF-kappa B, a transcription factor that plays a vital role in inflammatory response. [30] Also via A2B receptor activation, adenosine inhibits the proliferation of fibroblasts, vascular smooth muscle cell proliferation, and protein and collagen synthesis.…”

Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockade

“…In fact, adenosine is a potent anti-inflammatory agent with A 2A Rs triggering BOFF^signals in activated immune cells, which constitutes one of the most fundamental and immediate tissue-protecting mechanisms (reviewed in [295,296]). A 2A R agonists were even named Bthe most potent anti-inflammatory drug known to mankind.^Ac-cordingly, activation of A 2A Rs has been shown to confer a robust protection against tissue damage from ischemiaYreperfusion injury in different organ such as heart [297Y299], blood vessels [300], kidney [301,302], liver [303,304], lung [305,306], joints [307], skin [308,309], and even in the spinal cord [310,311] and in the brain following hemorrhage [312] or acute infection [313]. Thus, it is the activation (rather the blockade) of A 2A Rs that confers protection against damage triggered by inflammation in peripheral tissues, precisely the opposite of what is observed in the damaged adult brain.…”

Adenosine A 2A receptor is a unique angiogenic target of HIF-2α in pulmonary endothelial cells

“…Among the adenosine receptors, both adenosine A 2A and the related adenosine A 2B receptors have unique properties. The activated adenosine A 2A receptor can protect against tissue injury in heart (22), kidney (23), skin (24), spinal cord (25), vascular smooth muscle (26), and lung (27). Adenosine A 2A receptor also can exhibit antiinflammatory properties (28).…”