The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
A biosynthetic pathway for anandamide
Abstract
The endocannabinoid arachidonoyl ethanolamine (anandamide) is a lipid transmitter synthesized and released “on demand” by neurons in the brain. Anandamide is also generated by macrophages where its endotoxin (LPS)-induced synthesis has been implicated in the hypotension of septic shock and advanced liver cirrhosis. Anandamide can be generated from its membrane precursor, N -arachidonoyl phosphatidylethanolamine (NAPE) through cleavage by a phospholipase D (NAPE–PLD). Here we document a biosynthetic pathway for anandamide in mouse brain and RAW264.7 macrophages that involves the phospholipase C (PLC)-catalyzed cleavage of NAPE to generate a lipid, phosphoanandamide, which is subsequently dephosphorylated by phosphatases, including PTPN22, previously described as a protein tyrosine phosphatase. Bacterial endotoxin (LPS)-induced synthesis of anandamide in macrophages is mediated exclusively by the PLC/phosphatase pathway, which is up-regulated by LPS, whereas NAPE–PLD is down-regulated by LPS and functions as a salvage pathway of anandamide synthesis when the PLC/phosphatase pathway is compromised. Both PTPN22 and endocannabinoids have been implicated in autoimmune diseases, suggesting that the PLC/phosphatase pathway of anandamide synthesis may be a pharmacotherapeutic target.
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Cites
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Cited by
The Endocannabinoid System as an Emerging Target of Pharmacotherapy
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Metadata
- Authors
- Liu, J., Wang, L., Harvey-White, J., Osei-Hyiaman, D., Razdan, R., Gong, Q., Chan, A. C., Zhou, Z., Huang, B. X., Kim, H.-Y., & Kunos, G.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2006-09-05
- Volume
- 103
- Issue
- 36
- Pages
- 13345-13350
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2154142977
- Cited by
- 470
- References
- 31
- FWCI
- 25.47
- Type
- journal article
- Language
- en
- Open access
- closed
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- Liu, J., Wang, L., Harvey-White, J., Osei-Hyiaman, D., Razdan, R., Gong, Q., Chan, A. C., Zhou, Z., Huang, B. X., Kim, H.-Y., & Kunos, G. (2006). A biosynthetic pathway for anandamide. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0601832103
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