DISTRIBUTION AND CHARACTERIZATION OF ANANDAMIDE AMIDOHYDROLASE IN MOUSE-BRAIN AND LIVER

Anandamide (N-Arachidonoylethanolamine) amidohydrolase catalyzing hydr olysis of anandamide was characterized in mice. The enzymatic activity was highest in the liver, followed by the brain and testis. Negligibl e activity was found in heart, lung and spleen. The activity in brain and liver was mainly localized in the microsomal fractions. Kinetic ex periments demonstrated that Km (mu M) and Vmax (nmol/min/mg protein) f or the brain microsomes were 9.3 and 2.58, respectively, while those f or the hepatic microsomes were 180 and 18.9, respectively. The activit y in the microsomes from the liver and brain was markedly inhibited by Cu2+, Hg2+, Se4+ phenylmethylsulfonylfluoride and sodium dodecylsulfa te. Brain but not hepatic microsomal enzyme activity was inhibited by Delta(9)-tetrahydrocannabinol, cannabidiol and cannabinol. Kinetic par ameters demonstrated that the inhibition by the cannabinoids was compe titive in nature. Relatively high distribution of the enzyme activity in brain suggests an importance of the enzyme in the central nervous s ystem to regulate the neuromodulatory fatty-acid amides.