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Adenosine receptors and renal ischaemia reperfusion injury
Author(s) -
Rabadi M. M.,
Lee H. T.
Publication year - 2015
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12402
Subject(s) - medicine , acute kidney injury , adenosine , kidney , adenosine receptor , ischemia , renal ischemia , adenosine a3 receptor , inflammation , pharmacology , purinergic signalling , reperfusion injury , acute tubular necrosis , renal function , receptor , agonist
One of the frequent clinical complications that results in billions of dollars in healthcare costs annually in the United States is acute kidney injury ( AKI ). Ischaemia reperfusion ( IR ) injury is a major cause AKI . Unfortunately, no effective treatment or preventive measure for AKI exists. With increased surgical complexity coupled with increasing number of elderly, the incidence of AKI is becoming more frequent. Adenosine is a metabolic breakdown product of adenosine triphosphate ( ATP ) and contributes to the regulation of multiple physiological events. Extracellular adenosine activates four subtypes of adenosine receptors ( AR ) including A 1 AR , A 2 A AR , A 2 B AR and A 3 AR . In the kidney, adenosine regulates glomerular filtration rate, vascular tone, renin release and is an integrative part of tubular glomerular feedback signal to the afferent arterioles. In addition, each AR subtype powerfully modulates renal IR injury. The A 1 AR activation protects against ischaemic insult by reducing apoptosis, necrosis and inflammation. Activation of A 2 A AR protects against renal injury by modulating leucocyte‐mediated inflammation as well as directly reducing renal tubular inflammation. Activation of A 2 B AR acts via direct activation of renal parenchymal as well as renovascular receptors and is important in kidney preconditioning. Finally, activation of A 3 AR exacerbates renal damage following renal IR injury while A 3 AR antagonism attenuates renal damage following ischaemic insult. Latest body of research suggests that kidney AR modulation may be a promising approach to treat ischaemic AKI . This brief review focuses on the signalling pathways of adenosine in the kidney followed by the role for various AR modulations in protecting against ischaemic AKI .