Anandamide transport inhibition by the varmilloid agonist olvanil

The structural similarities between the anandamide transport inhibitor N-(4-hydroxyphenyl)-arachidonylamide (AM404) and the synthetic vanilloid agonist olvanil [(N-vanillyl)-9-oleamide], prompted us to investigate the possibility that olvanil may interfere with anandamide transport. The intracellular accumulation of [H-3]anandamide by human astrocytoma cells was prevented by olvanil with a K-i value of 14.1 +/- 7.1 mu M. By contrast, capsaicin [(8-methyl-N-vanillyl)-6-noneamide], a plant-derived vanilloid agonist, and capsazepine (N-[2-(4-chlorophenyl)ethyl]-1,3,4,5-tetrahydro-7,8-dihydroxy-2H-2-benzazepine-2-carbothioamide), a vanilloid antagonist, had no such effect (K-i > 100 mu M). These results indicate that, although less potent than AM404 (K-i 2.1 +/- 0.2 mu M), olvanil may reduce anandamide clearance at concentrations similar to those needed for vanilloid receptor activation. (C) 1999 Elsevier Science B.V. All rights reserved.