Administration of exogenous adenosine triphosphate to ischemic skeletal muscle induces an energy-sparing effect: Role of adenosine receptors

Claudio Maldonado, Sathnur B. Pushpakumar, Gustavo Perez-Abadia, Sengodagounder Arumugam, Andrew N. Lane

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Background: Ischemia-reperfusion injury is a devastating complication that occurs in allotransplantation and replantation of limbs. Over the years, several preservation strategies have been used to conserve the critical levels of intracellular adenosine triphosphate (ATP) during ischemia to sustain the ion gradients across the membranes and thus the tissue viability. The administration of exogenous ATP to ischemic tissues is known to provide beneficial effects during reperfusion, but it is unclear whether it provides protection during ischemia. The purpose of the present study was to determine the effect of ATP administration on high-energy phosphate levels in ischemic skeletal muscle and to examine the role of purinergic and adenosine receptors in mediating the response to exogenous ATP. Methods: The extensor digitorum longus muscles of Fischer rats were subjected to ischemia and treated with different concentrations of ATP with or without purinergic and adenosine receptor blockers. Phosphorus-31 nuclear magnetic resonance spectroscopy was used to measure the rate of decay of ATP, phosphocreatine (PCr), and the formation of adenosine monophosphate and acidification. Phosphorylated compounds were analyzed using a simple model of energy metabolism, and the PCr half-life was used as an index of internal depletion of ATP to distinguish between intracellular and extracellular ATP. Results: PCr decay was rapid in all muscle groups and was followed by gradual ATP decay. The half-life of PCr was significantly longer in the ATP-treated muscles than in the vehicle controls and was maximally prolonged by treating with slow hydrolyzing adenosine 5′-O-(3-thio)triphosphate. Purinoceptor (P2X) blockade with ATP treatment significantly increased the half-life of PCr, and adenosine receptor blockers blunted the response. Administration of adenosine to ischemic muscles significantly increased the half-life of PCr compared with that in the vehicle controls. Conclusions: Exogenous ATP administration to ischemic skeletal muscles appears to spare intracellular energy by acting primarily through adenosine receptors.

Original languageEnglish
Pages (from-to)E15-E22
JournalJournal of Surgical Research
Volume181
Issue number1
DOIs
StatePublished - May 1 2013

Bibliographical note

Funding Information:
This work was funded in part by grants from the National Institutes of Health and ( National Institutes of Health National Center for Research Resources grant 5P20RR018733 ), the Kentucky Challenge for Excellence , and the Brown Foundation . NMR spectra were recorded at the James Graham Brown Cancer Center NMR facility.

Keywords

  • ATP
  • Adenosine receptors
  • Adenosine triphosphate
  • Ischemia reperfusion injury
  • Nuclear magnetic resonance
  • Phosphocreatine
  • Purinoceptors
  • Skeletal muscle

ASJC Scopus subject areas

  • Surgery

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