Palmitoylethanolamide enhances anandamide stimulation of human vanilloid VR1 receptors

In human embryonic kidney cells over-expressing the human vanilloid recepto r type 1 (VR1), palmitoylethanolamide (PEA, 0.5-10 muM) enhanced the effect of arachidonoylethanolamide (AEA, 50 nM) on the VRI-mediated increase of t he intracellular Ca2+ concentration. PEA (5 muM) decreased the AEA half-max imal concentration for this effect from 0.44 to 0.22 muM. The PEA effect wa s not due to inhibition of AEA hydrolysis or adhesion to non-specific sites . since bovine serum albumin (0.01-0.25%) potently inhibited AEA activity, and PEA also enhanced the effect of low concentrations of the VR1 agonists resiniferatoxin and capsaicin. PEA (5 RM) enhanced the affinity of AEA for VR1 receptors as assessed in specific binding assays. These data suggest th at PEA might be an endogenous enhancer of VR1-mediated AEA actions. (C) 200 1 Published by Elsevier Science B.V. on behalf of the Federation of Europea n Biochemical Societies.