The properties of UDP-glucuronyltransferase for cannabinoids in rat liver microsomes.

Abstract

The glucuronidation of .DELTA.9-tetrahydrocannabinol (.DELTA.9-THC), cannabidiol (CBD) and cannabinol (CBN) in rat liver microsomes was studied. The enzyme activities for the cannabinoids were 26.3 (.DELTA.9-THC), 52.9 (CBD) and 104.8 (CBN) pmol/min per mg protein. The apparent Km values of UDP-glucuronyltransferase for the cannabinoids were 0.29 (.DELTA.9-THC), 0.18 (CBD) and 2.78 (CBN) mM, while Vmax were 40.3 (.DELTA.9-THC), 104.9 (CBD) and 593.3 (CBN) pmol/min per mg protein. Following treatment of rats with 3-methylcholanthrene, the enzyme activities for .DELTA.9-THC, CBD and CBN were increased 132, 43 and 1198%, respectively, whereas the corresponding increases in microsomes from phenobarbital-treated rats were 127, 13 and 97%, respectively. The cannabinoid glucuronidation was activated 2- to 3-fold by the addition of UDP-N-acetylglucosamine, but not activated by the addition of Triton X-100 in vitro. The properties of cannabinoid UDP-glucuronyltransferase were discussed.