Inhibition of anandamide amidase activity in mouse brain microsomes by cannabinoids.
Mouse brain microsomes contain an amidase that catalyzes the hydrolysis of N-arachidonylethanolamide to arachidonic acid and ethanolamine. The enzymatic activity is dependent on the protein concentration of the microsomes and observed over a wide range of pH, 7.4 to 9.5. Kinetic analysis indicated that K(m) (microM) and Vmax (nmol/min/mg protein) were 17.7 +/- 4.1 and 1.81 +/- 0.32, respectively. Cannabidiol (CBD), cannabinol (CBN) and delta 9-tetrahydrocannabinol (delta 9-THC) significantly inhibited the hydrolysis of the amide by mouse brain microsomes. At a concentration of 160 microM, the inhibitory potency decreased in the following order, CBD (66%) > CBN (46%) > delta 9-THC (31%).
Watanabe
K
K
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
Kayano
Y
Y
Matsunaga
T
T
Yamamoto
I
I
Yoshimura
H
H
D000581:Amidohydrolases / Q000037:antagonists & inhibitors*; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002186:Cannabinoids / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D008297:Male; D051379:Mice; D008861:Microsomes / Q000201:enzymology*
D002186:Cannabinoids; D000581:Amidohydrolases; C087226:arachidonoylethanolamide synthase