title: Adenosine reduces glutamate release in rat spinal synaptosomes.
abstract: BACKGROUND
  A1 adenosine receptor activation reduces hypersensitivity in animal models of chronic pain, but intrathecal adenosine does not produce analgesia to acute noxious stimuli. Here, the authors test whether increased inhibition by adenosine of glutamate release from afferents after injury accounts for this difference.
  
  
  METHODS
  Synaptosomes were prepared from the dorsal half of the lumbar spinal cord of normal rats or those with spinal nerve ligation. Glutamate release evoked by the TRPV-1 receptor agonist, capsaicin, was measured. Adenosine with or without adenosine A1 and A2 receptor antagonists was applied to determine the efficacy and mechanism of adenosine to reduce capsaicin-evoked glutamate release.
  
  
  RESULTS
  Capsaicin produced a concentration-dependent glutamate release similarly in normal and nerve-injured rats. Capsaicin-evoked glutamate release was inhibited by adenosine or R-PIA (R-N6-(2- phenylisopropyl)-adenosine) in a concentration-dependent manner, with a threshold of 10 nm in both normal and nerve-ligated synaptosomes. Blockade of capsaicin-evoked glutamate release by adenosine was reversed similarly in synaptosomes from normal and spinal nerve-ligated animals by an A1 adenosine receptor antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine) but not by an A2 adenosine receptor antagonist DMPX (3'7-dimethyl-1-proparaglyxanthine). Capsaicin-evoked glutamate release, as well as its inhibition by adenosine, did not differ between synaptosomes prepared from tissue ipsilateral and contralateral to spinal nerve ligation.
  
  
  CONCLUSIONS
  These observations confirm previous neurophysiologic studies that presynaptic adenosine A1 receptor activation inhibits glutamate release from primary afferents. This effect is unaltered after peripheral nerve injury and thereby is unlikely to account for the enhanced analgesic efficacy of intrathecal adenosine in this setting.
authors.affiliation: Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: Xinhui
authors.initials: X
authors.lastname: Li
authors.forename: James C
authors.initials: JC
authors.lastname: Eisenach
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D058916:Adenosine A1 Receptor Antagonists; D000818:Animals; D002211:Capsaicin / Q000037:antagonists & inhibitors; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D008026:Ligation; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013127:Spinal Nerves / Q000473:pathology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000187:drug effects
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D018698:Glutamic Acid; D000241:Adenosine; D002211:Capsaicin