adp-beta-s and Hypoxia

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.

Topics: Adenosine; Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Energy Metabolism; Hemolysis; Hypotonic Solutions; Hypoxia; Kidney Tubules, Proximal; Kinetics; L-Lactate Dehydrogenase; Male; Potassium; Quinazolines; Rats; Rats, Sprague-Dawley; Receptors, Purinergic P2; Thionucleotides; Triazoles