ATP protects, by way of receptor-mediated mechanisms, against hypoxia-induced injury in renal proximal tubules.
We examined the effect of ATP on hypoxia-induced injury in freshly isolated rat renal proximal tubules and compared it with the effects of stable ATP analogues and ATP degradation products. Extracellular ATP significantly reduced hypoxia-induced structural cell damage (lactate dehydrogenase release). P(2)-receptor agonistic ATP analogues, including 2'-methylthio-ATP (2-Me-S-ATP), were also protective. In contrast, the P(1)-agonistic degradation products AMP and adenosine were not protective. Hypoxia-induced functional cell damage (loss of cellular potassium) was not changed by ATP or 2-Me-S-ATP. We therefore conclude that the protective property of ATP is not based on an effect of the degradation products or on a direct effect on cellular energy metabolism. The data indicate that the protective effect of ATP is mediated by P(2) receptors.
Kribben
Andreas
A
Department of Nephrology and Hypertension, University Hospital Essen, Germany. andreas.kribben@uni-essen.de
Feldkamp
Thorsten
T
Horbelt
Markus
M
Lange
Bettina
B
Pietruck
Frank
F
Herget-Rosenthal
Stefan
S
Heemann
Uwe
U
Philipp
Thomas
T
D000241:Adenosine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000249:Adenosine Monophosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects; D006461:Hemolysis; D007038:Hypotonic Solutions; D000860:Hypoxia / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism*; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D011188:Potassium / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D013873:Thionucleotides / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
D007038:Hypotonic Solutions; D011799:Quinazolines; D018048:Receptors, Purinergic P2; D013873:Thionucleotides; D014230:Triazoles; C030812:adenosine 5'-O-(2-thiodiphosphate); C022571:adenosine 5'-O-(3-thiotriphosphate); D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D000241:Adenosine; D011188:Potassium; C008501:2-methylthio-ATP; C052410:9-chloro-2-(2-furyl)-(1,2,4)triazolo(1,5-c)quinazolin-5-imine