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Adenosine Receptors and the Kidney

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

Abstract

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.

Keywords

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 

Abbreviations

AA

Afferent arteriole

ADO

Adenosine

ARF

Acute renal failure

AXAR

Adenosine receptor subtype x

B

Bowman’s capsule

BG9719

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

BG9928

1,3-Dipropyl-8-[1-(4-propionate)-bicyclo-[2,2,2]octyl)]xanthine

BM

Basement membrane

BS

Bowman’s space

cAMP

Cyclic adenosine monophosphate

CD39

Ecto-nucleoside triphosphate diphosphohydrolase-1

CD73

Ecto-5 -nucleotidase

CGS21680

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

CVT-124

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

DMPX

3,7-Dimethyl-1-propargylxanthine

DPCPX

1,3-Dipropyl-8-cyclopentylxanthine

DPSPX

1,3-Dipropyl-8-sulfophenylxanthine

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

EA

Efferent arteriole

EGM

Extraglomerular mesangium

ENTPDase

Ectonucleoside triphosphate diphosphohydrolase

FK-453

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

FK-838

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

GFR

Glomerular filtration rate

HSP27

Heat-shock protein 27

IMCD

Inner medullary collecting duct

KW-3902

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

MBF

Medullary blood flow

MC

Mesangium cells

mTAL

Medullary thick ascending limb

NHE

Na+ − H+ exchanger

NKCC2

Na+ − K+ − 2Cl- cotransporter

NO

Nitric oxide

NY2HA

New York Heart Association

pO2

Partial oxygen pressure

PT

Proximal tubule

SNGFR

Single nephron glomerular filtration rate

TAL

Thick ascending limb

TGF

Tubuloglomerular feedback

TNa

Transport of sodium

VSMC

Vascular smooth muscle cells

Notes

Acknowledgements

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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