title: [3H]alpha,beta-methylene ATP binding to P2X purinoceptor is unaffected by volatile anaesthetics.
abstract: OBJECTIVE
  The P2X receptor is responsible for fast excitatory neurotransmission in the central nervous system. This receptor is suggested as one of the targets of volatile anaesthetics. The study was undertaken to examine the site of action of volatile anaesthetics, especially for P2X purinoceptor-mediated neurotransmission.
  
  
  METHODS
  The effect of sevoflurane and isoflurane on [3H]alpha,beta-methylene ATP binding was investigated in rat crude synaptic membranes. The crude synaptic membranes were prepared from Sprague-Dawley rat brains by centrifugation and then incubated with volatile anaesthetics or P2 receptor antagonists.
  
  
  RESULTS
  [3H]alpha,beta-methylene ATP binding was unchanged by either sevoflurane or isoflurane at clinically relevant concentrations. Suramin, a P2 antagonist, significantly (P < 0.05) decreased the binding of [3H]alpha,beta-methylene ATP in a dose-dependent manner (68.7 +/- 14.7% at 10 micromol, 49.5 +/- 6.4% at 50 micromol, 24.3 +/- 5.7% at 100 micromol, n = 10, mean +/- SD), whereas pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), another P2 antagonist, did not affect the binding.
  
  
  CONCLUSIONS
  The suppressive effect of volatile anaesthetics on ATP-mediated excitatory synaptic transmission could be one site of action. However, the blockade of ATP binding to P2X receptors is not a mechanism of action of volatile anaesthetics.
authors.affiliation: Jikei University School of Medicine, Department of Pharmacology, Tokyo, Japan. ejmasaki@jikei.ac.jp
authors.forename: E
authors.initials: E
authors.lastname: Masaki
authors.forename: K
authors.initials: K
authors.lastname: Yamazaki
authors.forename: S
authors.initials: S
authors.lastname: Hori
authors.forename: M
authors.initials: M
authors.lastname: Kawamura
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000378:metabolism*; D000704:Analysis of Variance; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007530:Isoflurane / Q000494:pharmacology; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000187:drug effects*; D000077149:Sevoflurane; D013498:Suramin / Q000008:administration & dosage / Q000494:pharmacology; D013570:Synaptic Membranes / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D014316:Tritium
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D058919:Purinergic P2 Receptor Antagonists; D019275:Radiopharmaceuticals; D018048:Receptors, Purinergic P2; D014316:Tritium; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D000077149:Sevoflurane; D011732:Pyridoxal Phosphate; D013498:Suramin; D000255:Adenosine Triphosphate; D007530:Isoflurane; C002630:alpha,beta-methyleneadenosine 5'-triphosphate