Δ9-Tetrahydrocannabinol, a major psychoactive constituent of marijuana, interacts with specific receptors, i.e. the cannabinoid receptors, thereby eliciting a variety of pharmacological responses. To date, two types of cannabinoid receptors have been identified: the CB1 receptor, which is abundantly expressed in the nervous system, and the CB2 receptor, which is predominantly expressed in the immune system. Previously, we investigated in detail the structure–activity relationship of various cannabinoid receptor ligands and found that 2-AG (2-arachidonoylglycerol) is the most efficacious agonist. We have proposed that 2-AG is the true natural ligand for both the CB1 and CB2 receptors. Despite the potential physiological importance of 2-AG, not much information is available concerning its biological activities towards mammalian tissues and cells. In the present study, we examined the effect of 2-AG on morphology as well as the actin filament system in differentiated HL-60 cells, which express the CB2 receptor. We found that 2-AG induces rapid morphological changes such as the extension of pseudopods. We also found that it provokes a rapid actin polymerization in these cells. Actin polymerization induced by 2-AG was abolished when cells were treated with SR144528, a CB2 receptor antagonist, and pertussis toxin, suggesting that the response was mediated by the CB2 receptor and Gi/o. A phosphoinositide 3-kinase, Rho family small G-proteins and a tyrosine kinase were also suggested to be involved. Reorganization of the actin filament system is known to be indispensable for a variety of cellular events; it is possible that 2-AG plays physiologically essential roles in various inflammatory cells and immune-competent cells by inducing a rapid actin rearrangement.
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Research Article|
March 08 2005
2-Arachidonoylglycerol, an endogenous cannabinoid receptor ligand, induces rapid actin polymerization in HL-60 cells differentiated into macrophage-like cells
Maiko GOKOH;
Maiko GOKOH
*Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-0195, Japan
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Seishi KISHIMOTO;
Seishi KISHIMOTO
*Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-0195, Japan
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Saori OKA;
Saori OKA
*Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-0195, Japan
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Masahiro MORI;
Masahiro MORI
*Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-0195, Japan
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Keizo WAKU;
Keizo WAKU
*Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-0195, Japan
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Yoshio ISHIMA;
Yoshio ISHIMA
†Ishima Institute for Neurosciences, Kunitachi, Tokyo 186-0002, Japan
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Takayuki SUGIURA
Takayuki SUGIURA
1
*Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-0195, Japan
1To whom correspondence should be addressed (email sugiurat@pharm.teikyo-u.ac.jp).
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Publisher: Portland Press Ltd
Received:
July 08 2004
Revision Received:
September 07 2004
Accepted:
September 30 2004
Accepted Manuscript online:
September 30 2004
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2005
Biochem J (2005) 386 (3): 583–589.
Article history
Received:
July 08 2004
Revision Received:
September 07 2004
Accepted:
September 30 2004
Accepted Manuscript online:
September 30 2004
Citation
Maiko GOKOH, Seishi KISHIMOTO, Saori OKA, Masahiro MORI, Keizo WAKU, Yoshio ISHIMA, Takayuki SUGIURA; 2-Arachidonoylglycerol, an endogenous cannabinoid receptor ligand, induces rapid actin polymerization in HL-60 cells differentiated into macrophage-like cells. Biochem J 15 March 2005; 386 (3): 583–589. doi: https://doi.org/10.1042/BJ20041163
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