1: Neuropharmacology. 2005 Jun;48(8):1079-85. 

A second N-acylethanolamine hydrolase in mammalian tissues.

Ueda N, Tsuboi K, Lambert DM.

Department of Biochemistry, Kagawa University School of Medicine, 1750-1
Ikenobe, Miki, Kagawa 761-0793, Japan.

It is widely accepted that fatty acid amide hydrolase (FAAH) plays a central
role in the hydrolysis of anandamide. However, we found a second
N-acylethanolamine hydrolase in animal tissues which hydrolyzed anandamide at
acidic pH. This "acid amidase" was first detected with the particulate fraction
of human megakaryoblastic CMK cells, and was solubilized by freezing and thawing
without detergent. The enzyme was distinguishable from FAAH in terms of (1) the
optimal activity at pH 5, (2) stimulation by dithiothreitol, (3) low sensitivity
to two FAAH inhibitors (methyl arachidonyl fluorophosphonate and
phenylmethylsulfonyl fluoride), and (4) high content in lung, spleen and
macrophages of rat. The acid amidase purified from rat lung was the most active
with N-palmitoylethanolamine among various long-chain N-acylethanolamines. To
develop specific inhibitors for this enzyme, we screened various analogues of
N-palmitoylethanolamine. Among the tested compounds,
N-cyclohexanecarbonylpentadecylamine was the most potent inhibitor which
does-dependently inhibited the enzyme with an IC(50) value of 4.5muM without
inhibiting FAAH at concentrations up to 100muM. The inhibitor was a useful tool
to distinguish the acid amidase from FAAH with rat basophilic leukemia (RBL-1)
cells that express both the enzymes.

PMID: 15910884 [PubMed - in process]