Adenosine Receptors and the Kidney

  • Volker VallonEmail author
  • Hartmut Osswald
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 193)


The autacoid, adenosine, is present in the normoxic kidney and generated in the cytosol as well as at extracellular sites. The rate of adenosine formation is enhanced when the rate of ATP hydrolysis prevails over the rate of ATP synthesis during increased tubular transport work or during oxygen deficiency. Extracellular adenosine acts on adenosine receptor subtypes (A1, A2A, A2B, and A3) in the cell membranes to affect vascular and tubular functions. Adenosine lowers glomerular filtration rate by constricting afferent arterioles, especially in superficial nephrons, and thus lowers the salt load and transport work of the kidney consistent with the concept of metabolic control of organ function. In contrast, it leads to vasodilation in the deep cortex and the semihypoxic medulla, and exerts differential effects on NaCl transport along the tubular and collecting duct system. These vascular and tubular effects point to a prominent role of adenosine and its receptors in the intrarenal metabolic regulation of kidney function, and, together with its role in inflammatory processes, form the basis for potential therapeutic approaches in radiocontrast media-induced acute renal failure, ischemia reperfusion injury, and in patients with cardiorenal failure.


Adenosine receptors Kidney Tubuloglomerular feedback Renin Fluid and electrolyte transport Metabolic control Acute renal failure Acute kidney injury Radiocontrast media Ischemia reperfusion injury Heart failure 



Afferent arteriole




Acute renal failure


Adenosine receptor subtype x


Bowman’s capsule


1,3-Dipropyl-8-[2-(5,6-epoxynorbornyl)] xanthine




Basement membrane


Bowman’s space


Cyclic adenosine monophosphate


Ecto-nucleoside triphosphate diphosphohydrolase-1


Ecto-5 -nucleotidase


2-[p-(2-Carboxyethyl)phenethylamino]-5 -N-ethylcarboxamido adenosine


S-Enantiomer of 1,3-dipropyl-8-[2-(5,6-epoxynorbornyl)] 1xanthine







DWH 146e

4-(3-(6-Amino-9-(5-ethylcarbamoyl-3,4-dihydroxytetrahydrofuran-2-yl)-9H-purin-2-yl)prop-2-ynyl)cyclohexanecarboxylic acid methyl ester


Efferent arteriole


Extraglomerular mesangium


Ectonucleoside triphosphate diphosphohydrolase


(+)-(R)-[(E)-3-(2-Phenylpyrazolo[1,5-a]pyridin-3-yl)acryloyl]-2-piperidine ethanol


6-Oxo-3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-1(6H)-pyridazinebutanoic ‘acid


Glomerular filtration rate


Heat-shock protein 27


Inner medullary collecting duct


8-(Noradamantan-3-yl)-1,3 dipropylxanthine


Medullary blood flow


Mesangium cells


Medullary thick ascending limb


Na+ − H+ exchanger


Na+ − K+ − 2Cl- cotransporter


Nitric oxide


New York Heart Association


Partial oxygen pressure


Proximal tubule


Single nephron glomerular filtration rate


Thick ascending limb


Tubuloglomerular feedback


Transport of sodium


Vascular smooth muscle cells



The work from our laboratories was supported by the Deutsche Forschungsgemeinschaft (DFG VA 118/2-1, DFG OS 42/1–42/7), the Department of Veterans Affairs, the National Institutes of Health (DK56248, DK28602, GM66232, P30DK079337), and the American Heart Association (GiA 655232Y).


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© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  1. 1.Departments of Medicine and PharmacologyUniversity of California San Diego and VA San Diego Healthcare SystemSan DiegoUSA
  2. 2.Department of Pharmacology, Medical FacultyUniversity of TübingenTübingenFederal Republic of Germany

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