Inhibition of cyclooxygenase-2 potentiates retrograde endocannabinoid effects in hippocampus

Nat Neurosci. 2004 Jul;7(7):697-8. doi: 10.1038/nn1262. Epub 2004 Jun 6.

Abstract

In hippocampal pyramidal cells, a rise in Ca(2+) releases endocannabinoids that activate the presynaptic cannabinoid receptor (CB1R) and transiently reduce GABAergic transmission-a process called depolarization-induced suppression of inhibition (DSI). The mechanism that limits the duration of endocannabinoid action in intact cells is unknown. Here we show that inhibition of cyclooxygenase-2 (COX-2), not fatty acid amide hydrolase (FAAH), prolongs DSI, suggesting that COX-2 limits endocannabinoid action.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amidohydrolases / antagonists & inhibitors
  • Amidohydrolases / pharmacology
  • Animals
  • Arachidonic Acids / pharmacology
  • Cannabinoid Receptor Modulators / pharmacology*
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / pharmacology*
  • Drug Synergism
  • Endocannabinoids*
  • Enzyme Inhibitors / pharmacology
  • Glycerides / pharmacology
  • Hippocampus / cytology*
  • In Vitro Techniques
  • Isoenzymes / antagonists & inhibitors*
  • Male
  • Meloxicam
  • Membrane Potentials / drug effects
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology
  • Patch-Clamp Techniques / methods
  • Piperidines / pharmacology
  • Polyunsaturated Alkamides
  • Prostaglandin-Endoperoxide Synthases
  • Pyramidal Cells / drug effects*
  • Pyramidal Cells / physiology
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Sulfonamides / pharmacology
  • Thiazines / pharmacology
  • Thiazoles / pharmacology

Substances

  • Arachidonic Acids
  • Cannabinoid Receptor Modulators
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Endocannabinoids
  • Enzyme Inhibitors
  • Glycerides
  • Isoenzymes
  • Piperidines
  • Polyunsaturated Alkamides
  • Pyrazoles
  • Sulfonamides
  • Thiazines
  • Thiazoles
  • AM 251
  • glyceryl 2-arachidonate
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Amidohydrolases
  • fatty-acid amide hydrolase
  • anandamide
  • nimesulide
  • Meloxicam