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Cellular and Molecular Life Sciences CMLS

, Volume 60, Issue 6, pp 1200–1208 | Cite as

Anandamide induces cell death independently of cannabinoid receptors or vanilloid receptor 1: possible involvement of lipid rafts

  • K. P. Sarker
  • I. Maruyama
Research Article

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.

Key words: Anandamide; cannabinoid receptor; vanilloid receptor 1; lipid raft; apoptosis. 

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Copyright information

© Birkhäuser Verlag, 2003

Authors and Affiliations

  • K. P. Sarker
    • 1
  • I. Maruyama
    • 1
  1. 1.Department of Laboratory and Molecular Medicine, Faculty of Medicine, Kagoshima University, Kagoshima 890 (Japan)JP

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