Regulation of anandamide tissue levels by N-arachidonylglycine

• Published in: Biochemical pharmacology Vol. 64; no. 7; pp. 1147 - 1150
• Main Authors: Burstein, Sumner H., Huang, Susan M., Petros, Timothy J., Rossetti, Ronald G., Walker, J Michael, Zurier, Robert B.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.10.2002; Elsevier Science
• Subjects: Analgesics; Anandamide; Animals; Arachidonic Acids - metabolism; Arachidonic Acids - pharmacology; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Cannabinoid Receptor Modulators; Cells, Cultured; Endocannabinoids; Glycine - analogs & derivatives; Glycine - pharmacology; Mass spectrometry; Medical sciences; Mice; Monocytes - drug effects; Monocytes - metabolism; N-Arachidonylglycine; Neuropharmacology; Pharmacology. Drug treatments; Polyunsaturated Alkamides; Rats; RAW cells; FAAH, fatty acid amide hydrolase; Rats; RAW cells; Mass spectrometry; and NAGly, N-arachidonylglycine; Anandamide; N-Arachidonylglycine; Rat; Rodentia; Antiinflammatory agent; Oral administration; Arachidonic acid; Cannabinoid; Glycine; In vitro; In vivo; Vertebrata; Mammalia; Analgesic; Analog; Animal; Established cell line; Mechanism of action
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/S0006-2952(02)01301-1

N-Arachidonylglycine (NAGly), the carboxylic analog of the endocannabinoid anandamide, occurs in rat and bovine brain as well as in peripheral sites and shows activity against tonic, formalin-induced pain. It was also observed, using cell membrane preparations, that it inhibits the hydrolytic activity of fatty acid amide hydrolase (FAAH) on anandamide ( N-arachidonylethanolamide). These data suggested that it may serve as an endogenous regulator of tissue anandamide concentrations. In this report, we show findings derived from mass spectrometric analyses, indicating that blood levels of anandamide in rats given 10 mg/kg p.o. of NAGly were increased significantly by more than 9-fold when compared with vehicle-treated controls. In vitro evidence in RAW 264.7 cells using a deuterium-labeled NAGly demonstrated that it was not a precursor or source of arachidonic acid for the observed 50% rise in anandamide levels, suggesting that the increase was due to some effect other than increased biosynthesis of anandamide. Moreover, the findings presented here suggest that NAGly can serve as a model for the design of agents to provide pharmacological control of tissue anandamide concentrations.