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Related Experiment Videos

A biosynthetic pathway for anandamide.

Jie Liu1, Lei Wang, Judith Harvey-White

  • 1Laboratories of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA. jiel@mail.nih.gov

Proceedings of the National Academy of Sciences of the United States of America
|August 30, 2006
PubMed
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A new pathway for synthesizing anandamide (a brain lipid transmitter) involves phospholipase C (PLC) and phosphatases, distinct from the previously known NAPE-PLD pathway. This PLC/phosphatase route is key for endotoxin-induced anandamide production in macrophages.

Area of Science:

  • Biochemistry
  • Neuroscience
  • Immunology

Background:

  • Anandamide (arachidonoyl ethanolamine) is a crucial endocannabinoid lipid transmitter synthesized on demand in the brain.
  • Endotoxin (LPS)-induced anandamide synthesis in macrophages is linked to septic shock and liver cirrhosis.
  • Anandamide is typically synthesized from N-arachidonoyl phosphatidylethanolamine (NAPE) via NAPE-PLD.

Purpose of the Study:

  • To identify and characterize an alternative biosynthetic pathway for anandamide.
  • To investigate the role of this new pathway in macrophage anandamide synthesis.
  • To explore the implications of this pathway in disease and as a therapeutic target.

Main Methods:

  • Investigated anandamide biosynthesis in mouse brain and RAW264.7 macrophages.

Related Experiment Videos

  • Utilized phospholipase C (PLC) and phosphatase assays to identify key enzymes.
  • Examined the regulation of anandamide pathways by lipopolysaccharide (LPS).

    • Main Results:

    • Discovered a novel pathway involving PLC cleavage of NAPE to phosphoanandamide, followed by dephosphorylation by phosphatases like PTPN22.
    • Demonstrated that LPS exclusively up-regulates the PLC/phosphatase pathway for anandamide synthesis in macrophages.
    • Showed that NAPE-PLD is down-regulated by LPS and acts as a salvage pathway.

    Conclusions:

    • The PLC/phosphatase pathway is the primary route for LPS-induced anandamide synthesis in macrophages.
    • PTPN22 and endocannabinoids are implicated in autoimmune diseases, suggesting therapeutic potential.
    • The PLC/phosphatase pathway represents a potential pharmacotherapeutic target for related conditions.