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Adenosine Receptors and the Kidney

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Adenosine Receptors in Health and Disease

Part of the book series: Handbook of Experimental Pharmacology ((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.

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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

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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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  1. Departments of Medicine and Pharmacology, University of California San Diego and VA San Diego Healthcare System, 3350 La Jolla Village Dr (9151), San Diego, CA, 92161, USA

    Volker Vallon

  2. Department of Pharmacology, Medical Faculty, University of Tübingen, Wilhelmstrasse 56, 72074, Tübingen, Federal Republic of Germany

    Hartmut Osswald

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    Constance N. Wilson

  2. Health Sciences Center, West Virginia University, Health Sciences S. 2267, Morgantown, 26506-9104, U.S.A.

    S. Jamal Mustafa

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Vallon, V., Osswald, H. (2009). Adenosine Receptors and the Kidney. In: Wilson, C., Mustafa, S. (eds) Adenosine Receptors in Health and Disease. Handbook of Experimental Pharmacology, vol 193. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-89615-9_15

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