Abstract:
Anandamide triggers various cellular activities by binding to cannabinboid (CB1/CB2) receptors or vanilloid receptor 1 (VR1). However, the role of these receptors in anandamide-induced apoptosis remains largely unknown. Here, we show that SR141716A, a specific inhibitor of cannabinoid receptor (CB1-R), did not block anandamide-induced cell death in endogenously CB1-R expressing cells. In addition, CB1-R-lacking Chinese hamster ovary (CHO) cells underwent cell death after anandamide treatment. SR144528, a specific inhibitor of CB2-R also failed to block anandamide-induced cell death in HL-60 cells. Capsazepine, a specific antagonist of VR1 could not prevent anandamide-induced cell death in constitutively and endogenously VR1 expressing PC12 cells. Moreover, anandamide noticeably triggered cell death in VR1-lacking human embryonic kidney (HEK) cells. In contrast, methyl-β cyclodextrin (MCD), a membrane cholesterol depletor, completely blocked anandamide-induced cell death in a variety of cells, including PC12, C6, Neuro-2a, CHO, HEK, SMC, Jurkat and HL-60 cells. MCD also blocked anandamide-induced superoxide generation, phosphatidyl serine exposure and p38 MAPK/JNK activation. Thus, our data imply a novel role for of membrane lipid rafts in anandamide-induced cell death.
Similar content being viewed by others
Author information
Authors and Affiliations
Additional information
Received 12 February 2003; accepted 21 March 2003
RID="*"
ID="*"Corresponding author.
RID="**"
ID="**"Reprint requests: rinken@m3.kufm.kagoshima-u.ac.jp
Rights and permissions
About this article
Cite this article
Sarker, K., Maruyama, I. Anandamide induces cell death independently of cannabinoid receptors or vanilloid receptor 1: possible involvement of lipid rafts. CMLS, Cell. Mol. Life Sci. 60, 1200–1208 (2003). https://doi.org/10.1007/s00018-003-3055-2
Issue Date:
DOI: https://doi.org/10.1007/s00018-003-3055-2