BML‐190 and AM251 act as inverse agonists at the human cannabinoid CB2 receptor: signalling via cAMP and inositol phosphates

FEBS Letters

New, David C¹  Wong, Yung H¹ 

[1] Department of Biochemistry, Molecular Neuroscience Center, and Biotechnology Research Institute, Hong Kong University of Science and Technology, Clearwater Bay, Hong Kong, PR China

关键词: BML-190;    AM251;    Cannabinoid;    CB2;    Inverse agonist;    AM251;    N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2;    3-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide;    AM630;    6-iodopravadoline;    BML-190;    indomethacin morpholinylamide;    FBS;    fetal bovine serum;    HEK;    human embryonic kidney;    IP;    inositol phosphates;    JWH 015;    (2-methyl-1-propyl-1H-indol-3-yl)-1-naphthalenylmethanone;    MEM;    minimum essential medium;    PLC;    phospholipase Cβ;    WIN 55;    212-2;    R(+)-[2;    3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo-[1;    2;    3-de]-1;    4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate;   

DOI  :  10.1016/S0014-5793(03)00048-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The aminoalkylindole BML-190 and diarylpyrazole AM251 ligands have previously been shown to bind to cannabinoid CB₂ and CB₁ receptors, respectively. In HEK-293 cells stably expressing the human CB₂ receptor, BML-190 and AM251 potentiated the forskolin-stimulated accumulation of cAMP. Moreover, the CB₂ receptor can interact productively with 16z44, a promiscuous Gα_16/z chimera. BML-190 and AM251 reduce the basal levels of inositol phosphate production in cells expressing the CB₂ receptor and 16z44. These results demonstrate that BML-190 and AM251 act as inverse agonists at the human CB₂ receptor acting via Gα_i/o and Gα_q family-coupled pathways.

【 授权许可】

Unknown