Evidence that 2-arachidonoylglycerol but not N-palmitoylethanolamine or anandamide is the physiological ligand for the cannabinoid CB2 receptor. Comparison of the agonistic activities of various cannabinoid receptor ligands in HL-60 cells

Takayuki Sugiura, Sachiko Kondo, Seishi Kishimoto, Tomoyuki Miyashita, Shinji Nakane, Tomoko Kodaka, Yoshitomo Suhara, Hiroaki Takayama, Keizo Waku

研究成果: Article査読

317 被引用数 (Scopus)

抄録

We examined the effect of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, on the intracellular free Ca2+ concentrations in HL-60 cells that express the cannabinoid CB2 receptor. We found that 2- arachidonoylglycerol induces a rapid transient increase in intracellular free Ca2+ concentrations in HL-60 cells. The response was affected by neither cyclooxygenase inhibitors nor lipoxygenase inhibitors, suggesting that arachidonic acid metabolites are not involved. Consistent with this notion, free arachidonic acid was devoid of any agonistic activity. Importantly, the Ca2+ transient induced by 2-arachidonoylglycerol was blocked by pretreatment of the cells with SR144528, a CB2 receptor-specific antagonist, but not with SR141716A, a CB1 receptor-specific antagonist, indicating the involvement of the CB2 receptor but not the CB1 receptor in this cellular response. G(i) or G(o) is also assumed to be involved, because pertussis toxin treatment of the cells abolished the response. We further examined the structure-activity relationship. We found that 2-arachidonoylglycerol is the most potent compound among a number of naturally occurring cannabimimetic molecules. Interestingly, anandamide and N-palmitoylethanolamine, other putative endogenous ligands, were found to be a weak partial agonist and an inactive ligand, respectively. These results strongly suggest that the CB2 receptor is originally a 2-arachidonoylglycerol receptor, and 2- arachidonoylglycerol is the intrinsic natural ligand for the CB2 receptor that is abundant in the immune system.

本文言語English
ページ(範囲)605-612
ページ数8
ジャーナルJournal of Biological Chemistry
275
1
DOI
出版ステータスPublished - 2000 1 7
外部発表はい

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

フィンガープリント 「Evidence that 2-arachidonoylglycerol but not N-palmitoylethanolamine or anandamide is the physiological ligand for the cannabinoid CB2 receptor. Comparison of the agonistic activities of various cannabinoid receptor ligands in HL-60 cells」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

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