2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, induces rapid actin polymerization in HL-60 cells differentiated into macrophage-like cells

• Published in: Biochemical journal 2005-03, Vol.386 (Pt 3), p.583-589
• Main Authors: Gokoh, Maiko, Kishimoto, Seishi, Oka, Saori, Mori, Masahiro, Waku, Keizo, Ishima, Yoshio, Sugiura, Takayuki
• Format: Article
• Language: English
• Subjects: Actins - chemistry; Actins - metabolism; ADP Ribose Transferases - metabolism; ADP Ribose Transferases - pharmacology; Arachidonic Acids - chemistry; Arachidonic Acids - metabolism; Arachidonic Acids - pharmacology; Biopolymers - chemistry; Biopolymers - metabolism; Botulinum Toxins - metabolism; Botulinum Toxins - pharmacology; Cannabinoid Receptor Agonists; Cannabinoid Receptor Antagonists; Cell Differentiation - drug effects; Cell Shape - drug effects; Endocannabinoids; Glycerides - chemistry; Glycerides - metabolism; Glycerides - pharmacology; HL-60 Cells; Humans; Ligands; Macrophages - cytology; Macrophages - drug effects; Macrophages - metabolism; Peptides, Cyclic; Protein Structure, Quaternary - drug effects; Receptors, Cannabinoid - metabolism; Time Factors
• ISSN: 0264-6021; 1470-8728
• DOI: 10.1042/BJ20041163

Delta9-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 G(i/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.