Localization of N‐acyl phosphatidylethanolamine phospholipase D (NAPE‐PLD) expression in mouse brain: A new perspective on N‐acylethanolamines as neural signaling molecules

  title={Localization of N‐acyl phosphatidylethanolamine phospholipase D (NAPE‐PLD) expression in mouse brain: A new perspective on N‐acylethanolamines as neural signaling molecules},
  author={Michaela Egertov{\'a} and Gabriel M. Simon and Benjamin F. Cravatt and Maurice R. Elphick},
  journal={Journal of Comparative Neurology},
N‐acylethanolamines (NAEs) are membrane‐derived lipids that are utilized as signaling molecules in the nervous system (e.g., the endocannabinoid anandamide). An N‐acyl phosphatidylethanolamine phospholipase D (NAPE‐PLD) that catalyzes formation of NAEs was recently identified as a member of the zinc metallohydrolase family of enzymes. NAPE‐PLD−/− mice have greatly reduced brain levels of long‐chain saturated NAEs but wild‐type levels of polyunsaturated NAEs (e.g., anandamide), suggesting an… 
Differential distribution of diacylglycerol lipase‐alpha and N‐acylphosphatidylethanolamine‐specific phospholipase d immunoreactivity in the superficial spinal dorsal horn of rats
The results suggest that both neurons and glial cells can synthesize and release 2‐AG and anandamide in the superficial spinal dorsal horn.
NAPE Phospholipase D Enzyme and Recent Advances in the Understanding of its Biological Properties
It is suggested that NAEs generated by NAPE-PLD in axons may act as anterograde synaptic signaling molecules that regulate the activity of postsynaptic neurons.
Localization of peroxisome proliferator-activated receptor alpha (PPARα) and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) in cells expressing the Ca2+-binding proteins calbindin, calretinin, and parvalbumin in the adult rat hippocampus
The hippocampal subpopulations of NAPE-PLD/PPARα-containing neurons that express selective Ca2+-binding proteins (CaBPs) should be considered when analyzing the role of NAEs/PParα-signaling system in the regulation of hippocampal functions.
Enzymological studies on the biosynthesis of N-acylethanolamines.
N-acylethanolamine metabolism with special reference to N-acylethanolamine-hydrolyzing acid amidase (NAAA).
Subcellular localization of NAPE-PLD and DAGL-α in the ventromedial nucleus of the hypothalamus by a preembedding immunogold method
Investigating the precise subcellular distribution of N-arachidonoylphospatidylethanolamine phospholipase D and DAGL-α in the dorsomedial VMH of wild-type mice supported the idea that the dorsal VMH displays the necessary machinery for the endocannabinoid-mediated modulation of synaptic transmission of brain circuitries that regulate important hypothalamic functions.
Cannabidiol's Upregulation of N-acyl Ethanolamines in the Central Nervous System Requires N-acyl Phosphatidyl Ethanolamine-Specific Phospholipase D
The hypothesis that cell lines representing cell types present in the central nervous system, neurons, astrocytes, and microglia would respond differently to THC, CBD, or their combination is tested.
Cannabinoid Receptor and N‐acyl Phosphatidylethanolamine Phospholipase D—Evidence for Altered Expression in Multiple Sclerosis
Findings from animal models suggest a role for the endocannabinoid system in the MS, particularly in the regulation of endothelial leukocyte adhesion and the cellular response to injury, which is supported by data from autopsy brain samples from patients with MS.
Enzymatic formation of anandamide.


Inactivation of N-acyl phosphatidylethanolamine phospholipase D reveals multiple mechanisms for the biosynthesis of endocannabinoids.
The illumination of distinct enzymatic pathways for the biosynthesis of long chain saturated and polyunsaturated NAEs suggests a strategy to control the activity of specific subsets of these lipids without globally affecting the function of the NAE family as a whole.
Regional distribution and age‐dependent expression of N‐acylphosphatidylethanolamine‐hydrolyzing phospholipase D in rat brain
Wide distribution of NAPE‐PLD in various brain regions and its age‐dependent expression is demonstrated, suggesting the central role of this enzyme in the formation of anandamide and other N‐acylethanolamines in the brain.
Discovery and Characterization of a Ca2+-independent Phosphatidylethanolamine N-Acyltransferase Generating the Anandamide Precursor and Its Congeners*
Results reveal that RLP-1 can function as a PE N-acyltransferase, catalytically distinguishable from the known Ca2+-dependent NAT.
Catabolism of N‐Acylethanolamine Phospholipids by Dog Brain Preparations
The phosphodiesterase showed an alkaline pH optimum and was also active towards N‐acetylphosphatidyletha‐nolamine, N‐acyl‐lysophosphati‐dylethanolamines, and glycerophospho(N‐ACYl)ethanolamine but showed little activity toward phosphatidylesthanolamine and phosphati‐dylcholine.
Pathways and mechanisms of N-acylethanolamine biosynthesis: can anandamide be generated selectively?
  • H. Schmid
  • Biology, Chemistry
    Chemistry and physics of lipids
  • 2000
Characterization and manipulation of the acyl chain selectivity of fatty acid amide hydrolase.
The significant changes in substrate selectivity achieved by single amino acid changes suggest that FAAH possesses a rather malleable substrate binding domain and may serve, along with other AS enzymes, as a template for the engineering of amidases with novel and/or tailored specificities.
A new perspective on cannabinoid signalling: complimentary localization of fatty acid amide hydrolase and the CB1 receptor in rat brain.
The close correspondence in the distribution of FAAH and CB1 in rat brain and the complimentary pattern of CB1 and FAAH expression at the cellular level provides important new evidence that FAAH may participate in cannabinoid signalling mechanisms of the brain.
Molecular Characterization of a Phospholipase D Generating Anandamide and Its Congeners*
It is confirmed that a specific phospholipase D is responsible for the generation of N-acylethanolamines including anandamide, strongly suggesting the physiological importance of lipid molecules of this class.
A biosynthetic pathway for anandamide
A biosynthetic pathway for anandamide in mouse brain and RAW264.7 macrophages is document 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.