Potentiation of the action of anandamide on hippocampal slices by the fatty acid amide hydrolase inhibitor, palmitylsulphonyl fluoride (AM 374)

Eur J Pharmacol. 1999 Oct 21;383(1):9-14. doi: 10.1016/s0014-2999(99)00609-3.

Abstract

The electrically-evoked release of [3H]acetylcholine from hippocampal brain slices is inhibited by cannabinoid receptor agonists. The effect of palmitylsulphonyl fluoride (AM 374), a recently developed inhibitor of fatty acid amide hydrolase, in influencing the potency of exogenously added anandamide in this preparation was examined. Anandamide alone had relatively little effect on [3H]acetylcholine release. By contrast, in the presence of AM 374 (0.1 microM), anandamide produced a significant inhibition of [3H]acetylcholine release at all concentrations tested (0.1-10 microM). In addition to experiments with AM 374 the effects of N-(4-hydroxyphenyl)arachidonamide (AM 404), a putative anandamide uptake inhibitor, was also examined. However, AM 404 at concentrations up to 10 microM, was not found to significantly enhance the effect of anandamide on electrically-evoked [3H]acetylcholine release. These results indicate that AM 374 potently inhibits endogenous amidase activity and thus facilitates access of exogenous anandamide to cannabinoid receptors in the hippocampal tissue.

Publication types

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

MeSH terms

  • Acetylcholine / metabolism
  • Amidohydrolases / antagonists & inhibitors*
  • Animals
  • Arachidonic Acids / pharmacology*
  • Benzoxazines
  • Cannabinoids / metabolism
  • Cyclohexanols / pharmacology
  • Drug Synergism
  • Electric Stimulation
  • Endocannabinoids
  • Enzyme Inhibitors / pharmacology*
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • In Vitro Techniques
  • Male
  • Morpholines / pharmacology
  • Naphthalenes / pharmacology
  • Palmitates / pharmacology*
  • Polyunsaturated Alkamides
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cannabinoid
  • Receptors, Drug / agonists

Substances

  • AM 374
  • Arachidonic Acids
  • Benzoxazines
  • Cannabinoids
  • Cyclohexanols
  • Endocannabinoids
  • Enzyme Inhibitors
  • Morpholines
  • Naphthalenes
  • Palmitates
  • Polyunsaturated Alkamides
  • Receptors, Cannabinoid
  • Receptors, Drug
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
  • 3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol
  • Amidohydrolases
  • fatty-acid amide hydrolase
  • Acetylcholine
  • anandamide
  • N-(4-hydroxyphenyl)arachidonylamide