Is the Cannabinoid CB1 Receptor a 2-Arachidonoylglycerol Receptor? Structural Requirements for Triggering a Ca2+ Transient in NG108-15 Cells.

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概要

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• The effects of Δ9-tetrahydrocannabinol and 2-arachidonoylglycerol on the intracellular free Ca2+ concentration ([Ca2+]1) in NG108-15 cells were examined in detail. We found that Δ9-tetrahydrocannabinol induces a rapid, modest increase in [Ca2+]i. The response was detectable with 3nM Δ9-tetrahydrocannabinol. We also found that very low concentrations of 2-arachidonoylglycerol elicit a rapid, more prominent increase in [Ca2+]1. Such a response was observed not only in NG108-15 cells but also in N18TG2 cells. The response induced by 2-arachidonoylglycerol in either NG108-15 cells or N18TG2 cells was abolished by pretreatment of the cells with a cannabinoid CB1 receptor-specific antagonist, SR141716A, suggesting that 2-arachidonoylglycerol interacts with the CB1 receptor to induce the response. The results of an experiment involving a phospholipase C inhibitor suggested that phospholipase C is involved in the rapid increase in [Ca2+]1 induced by 2-arachidonoylglycerol. We also found that 1 (3)-arachidonoylglycerol exhibits similar activity to that of 2-arachidonoylglycerol, although its activity at low concentrations was somewhat weak compared with that of 2-arachidonoylglycerol. We further confirmed that several structural analogues of 2-arachidonoylglycerol were less active compared with 2-arachidonoylglycerol. These results suggest that the structure of 2-arachidonoylglycerol is strictly recognized by the CB1 receptor, which raises the possibility that the CB1 receptor is originally a 2-arachidonoylglycerol receptor.

• 社団法人 日本生化学会の論文

著者

• Waku Keizo

  Faculty Of Pharmaceutical Science Teikyo University

• Sugiura Takayuki

  Faculty Of Pharmaceutical Sciences Teikyo University

• NAKANE Shinji

  Faculty of Pharmaceutical Sciences, Teikyo University

• Watanabe Kazuhito

  Faculty Of Pharmaceutical Sciences Hokuriku University

• Ishima Yoshio

  Ishima Institute For Neurosciences

• KONDO Sachiko

  Faculty of Pharmaceutical Sciences, Teikyo University

• KONDO Hironori

  Faculty of Pharmaceutical Sciences, Teikyo University

• Kodaka Tomoko

  Faculty Of Pharmaceutical Sciences Teikyo University

• Yamamotot Ikuo

  Faculty of Pharmaceutical Sciences, Hokuriku University

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