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

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.

Lysophosphatidic acid, a growth factor-like lipid, in the saliva.

Lysophosphatidic acid is a multifunctional phospholipid mediator and elicits a variety of biological responses in vitro and in vivo. Evidence is accumulating that lysophosphatidic acid plays important physiological roles in diverse mammalian tissues and cells. In the present study, we first examined whether lysophosphatidic acid is present in human saliva. We found that a significant amount of lysophosphatidic acid is present in the saliva (0.785 nmol/ml). The predominant fatty acyl moiety of lysophosphatidic acid was 18:1n-9 + n-7 followed by 18:0 and 16:0. A small amount of lysoplasmanic acid, an alkyl ether-linked analog of lysophosphatidic acid, was also detected in the saliva (0.104 nmol/ml). We found that physiologically relevant concentrations of lysophosphatidic acid induced accelerated growth of cells of mouth, pharynx, and esophagus origin in vitro. Lysophosphatidic acid also induced rapid increases in the intracellular free Ca2+ concentrations in these cells. We obtained evidence that lysophosphatidic acid receptor mRNAs are actually present in these cells. These results strongly suggest that lysophosphatidic acid is involved in wound healing in the upper digestive organs such as the mouth, pharynx, and esophagus.