Compertitive Inhibition of Δ8-Tetrahydrocannabinol and Its Active Metabolites for Cannabinoid Receptor Binding

Ikuo YAMAMOTO; Toshiyuki KIMURA; Ayako KAMEI; Hisatoshi YOSHIDA; Kazuhito WATANABE; Ing Kang HO; Hidetoshi YOSHIMURA

doi:10.1248/bpb.21.408

Compertitive Inhibition of Δ⁸-Tetrahydrocannabinol and Its Active Metabolites for Cannabinoid Receptor Binding

Ikuo YAMAMOTO, Toshiyuki KIMURA, Ayako KAMEI, Hisatoshi YOSHIDA, Kazuhito WATANABE, Ing Kang HO, Hidetoshi YOSHIMURA

著者情報

キーワード: active metabolite, 11-hydroxy-Δ⁸-THC, 11-oxo-Δ⁸-THC, CP-55940, cannabinoid receptor

ジャーナルフリー

1998 年 21 巻 4 号 p. 408-410

DOI https://doi.org/10.1248/bpb.21.408

詳細

抄録

In vitro binding characteristics of Δ⁸-tetrahydrocannabinol (Δ⁸-THC) and its metabolites, 11-hydroxy-Δ⁸-THC (11-OH-Δ⁸-THC) and 11-oxo-Δ⁸-THC, as well as an inactive metabolite, Δ⁸-THC-11-oic acid, as a cannabinoid receptor site from bovine cortex were examined using the specific agonist [³H]CP-55940. 11-OH-Δ⁸-THC and 11-oxo-Δ⁸-THC strongly inhibited the specific binding of [³H]CP-55940. The K_i values of 11-OH-Δ⁸-THC and 11-oxo-Δ⁸-THC for the specific binding of [³H]CP-55940 were 52 and 143 nM, respectively, whereas that of Δ⁸-THC-11-oic acid was 917 nM. Scatchard plot analyses indicated that 11-OH-Δ⁸-THC and 11-oxo-Δ⁸-THC caused a significant increase in the apparent K_D value without changing the apparent B_max. These results reveal that active metabolites of Δ⁸-THC also competitively bind to the cannabinoid receptor as agonists.

責任著者(Corresponding author)

J-STAGEへの登録はこちら（無料）