Abstract
Anandamide (arachidonoyl-ethanolamide, AnNH) was the first brain endogenous substance to be proposed as a physiological agonist at central cannabinoid receptors1. Apart from its cannabimimetic properties (recently reviewed in ref. 2), a role as a neuronal chemical signal for AnNH was suggested also by the finding of molecular mechanisms for its inactivation and Ca2+-dependent biosynthesis by rat central neurons3. The degradation of AnNH by neurons involves the enzymatic hydrolysis of its amide bond with formation of arachidonic acid (AA) and ethanolamine. The enzyme catalyzing this hydrolysis, originally named ‘anandamide amidohydrolase’, was characterized from rat4, 5 and porcine6 brain membranes and was found in high levels also in the liver4. The enzyme was inhibited by typical serine and cysteine protease inhibitors, and displayed a peculiar pH dependency profile with optimal activity at 8.5<pH<10.0. The interest towards AnNH amidohydrolase was increased further by the suggestion2, 8 that the same enzyme may also catalyze the hydrolysis of other bioactive acylethanolamides, such as the anti-inflammatory palmitoylethanolamide (PEA)7, and the primary fatty acid amide, cis-9-octadecenoamide (oleamide), a novel sleep-inducing factor in mammals9. The recent cloning and expression of rat liver ‘oleamide hydrolase’ cDNA10 confirmed that the same enzyme can hydrolyze both oleamide and, at a higher rate, AnNH8, leading to propose for this enzyme the name ‘fatty acid amide hydrolase’ (FAAH)8, 10. In this paper we report the preliminary characterization of FAAH-like enzymatic activities from a blood cell type, the rat basophilic leukemia (RBL-1) cell line, and from other peripheral mammalian and invertebrate cells, and describe the effect of five synthetic AA-derived inhibitors on these enzymes as well as on the previously described amidohydrolases from mouse neuroblastoma (N18TG2) cells8 and porcine brain6.
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De Petrocellis, L. et al. (1997). Brain and Peripheral Anandamide Amidohydrolase and Its Inhibition by Synthetic Arachidonate Analogues. In: Sinzinger, H., Samuelsson, B., Vane, J.R., Paoletti, R., Ramwell, P., Wong, P.YK. (eds) Recent Advances in Prostaglandin, Thromboxane, and Leukotriene Research. Advances in Experimental Medicine and Biology, vol 433. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-1810-9_55
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DOI: https://doi.org/10.1007/978-1-4899-1810-9_55
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