Paracetamol inhibits nitric oxide synthesis in murine spinal cord slices.
Paracetamol is an effective analgesic but its mechanism of action is unclear. We investigated the effect of paracetamol and the analgesic adjuvant caffeine on the activity of NO synthase in mouse spinal cord and cerebellar slices in vitro, by measuring the conversion of [(3)H]arginine to [(3)H]citrulline. Paracetamol (100 microM) had no effect on NO synthase activity in cerebellum, but in the spinal cord both paracetamol (100 microM) and caffeine (30 microM) attenuated glutamate (5 mM)-induced [(3)H]citrulline production and in combination they abolished it. In conclusion paracetamol inhibits spinal cord NO synthesis and this may be related to its analgesic effects.
Godfrey
Lisa
L
Pharmacology Group, School of Biomedical and Molecular Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK.
Bailey
Ian
I
Toms
Nick J
NJ
Clarke
Geoffrey D
GD
Kitchen
Ian
I
Hourani
Susanna M O
SM
D000082:Acetaminophen / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002956:Citrulline / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism
D018712:Analgesics, Non-Narcotic; D000697:Central Nervous System Stimulants; D004791:Enzyme Inhibitors; D002956:Citrulline; D009569:Nitric Oxide; D000082:Acetaminophen; D002110:Caffeine; D018698:Glutamic Acid; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester