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

The electrically-evoked release of [H-3]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 [H-3]acetylcholine release. By contrast, in the presence of AM 374 (0.1 mu M), anandamide produced a significant inhibition of [H-3]acetylcholine release at all concentrations tested (0.1-10 mu M). 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 mu M, was not found to significantly enhance the effect of anandamide on electrically-evoked [H-3]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. (C) 1999 Elsevier Science B.V. All rights reserved.