A biosynthetic pathway for anandamide

• DOI: 10.1073/pnas.0601832103
• Publication Date: 2006-08-28T22:10:40Z
• Authors: Jie Liu; Lei Wang; Judith Harvey-White; Douglas Osei-Hyiaman; Raj Razdan; Qian Gong; Andrew C. Chan; Zhifeng Zhou; Bill X. Huang; Hee-Yong Kim; George Kunos
• Keywords: Anandamide; 2-Arachidonoylglycerol; Phospholipase D

The endocannabinoid arachidonoyl ethanolamine (anandamide) is a lipid transmitter synthesized and released “on demand” by neurons in the brain. Anandamide also generated macrophages where its endotoxin (LPS)-induced synthesis has been implicated hypotension of septic shock advanced liver cirrhosis. can be from membrane precursor, N -arachidonoyl phosphatidylethanolamine (NAPE) through cleavage phospholipase D (NAPE–PLD). Here we document biosynthetic pathway for anandamide mouse brain RAW264.7 that involves C (PLC)-catalyzed NAPE to generate lipid, phosphoanandamide, which subsequently dephosphorylated phosphatases, including PTPN22, previously described as protein tyrosine phosphatase. Bacterial mediated exclusively PLC/phosphatase pathway, up-regulated LPS, whereas NAPE–PLD down-regulated LPS functions salvage when compromised. Both PTPN22 endocannabinoids have autoimmune diseases, suggesting may pharmacotherapeutic target.