Gene expression of NAPE phospholipase D enzyme and its role in hormonal regulation

NAPE phospholipase D

Abstract

N-acylethanolamines (NAEs) are membrane-derived lipids that are utilised as signaling molecules in the nervous system and elsewhere in the body. A N-Acylphosphatidylethanolamine Phospholipase D (NAPE-PLD) that catalyses formation of NAEs has been identified as a member of the zinc metallohydrolase family of enzymes. Intense NAPE-PLD immunoreactivity was also detected in axons of the vomeronasal nerve that project to the accessory olfactory bulb. NAPE-PLD expressionwas detected in other brain regions (e.g. hippocampus, cortex, thalamus, hypothalamus), but the intensity of immunostaining was weaker than in mossy fibres.Collectively, the data obtained indicate that NAPE-PLD is expressed by specific tissues in the body. Specific gene knock out animals have also been created. Recent cDNA cloning of the NAPE-hydrolyzing PLD (NAPEPLD) from mouse, rat and human revealed that NAPE-PLD is a novel enzyme which has no homology with any known PLD enzymes, but belongs to the zinc metallo-hydrolase family of the β-lactamase fold. The recombinant enzyme hydrolyzed various NAPEs, including the anandamide precursor N-arachidonoylphosphatidylethanolamine at similar rates, but was inactive with phosphatidylcholine and phosphatidylethanolamine. Considering cannabimimetic activities of anandamide, the enzymes involved in the biosynthesis and degradation of anandamide, including NAPE-PLD, may be promising targets for therapeutic agents.