{
  "id": 9228266,
  "title": "A phytocannabinoid-sensitive phosphorylation switch converts endocannabinoids into alternative lipid GPCR activators",
  "url": "https://urgent.news/2026/09/22/a-phytocannabinoid-sensitive-phosphorylation-switch-converts",
  "topic": "science",
  "section": "Science",
  "published": "2026-09-22T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.21.753239v1?rss=1"
  },
  "original_language": "en",
  "account": "Endocannabinoids, such as anandamide and 2-arachidonoylglycerol, are naturally occurring lipid molecules that interact with G protein-coupled receptors (GPCRs) named CB1 and CB2. Researchers have now discovered that phosphorylation of anandamide, a significant endocannabinoid, can transform it into an alternative lipid molecule that activates different types of receptors.\n\nThis study found that anandamide, when phosphorylated by an enzyme called diacylglycerol kinase theta (DGKq or DGKQ), becomes anandamide phosphate (AEAp). AEAp gains the ability to interact with lysophosphatidic acid (LPA) receptors (LPARs) and a primate-specific bile acid sensory receptor called MRGPRX4. The researchers identified DGKq as the kinase responsible for anandamide phosphorylation through various methods, such as activity-guided brain fractionation, inhibitor profiling, and recombinant reconstitution.\n\nInterestingly, DGKq was found to exhibit noncanonical biphasic lipid kinetics, meaning its activity varied depending on the type of lipid it was interacting with. Additionally, DGKq was inhibited by phytocannabinoids, which are compounds found in the Cannabis plant. Among these phytocannabinoids, tetrahydrocannabinolic acid (THC-A) was particularly effective at inhibiting DGKq's activity.\n\nThis research highlights the versatility of endocannabinoids, demonstrating that they are not only receptors for cannabinoids but also adaptable lipid signals that can activate different types of GPCRs. The study bridges the gap between lipid metabolism and Cannabis pharmacology, shedding light on the potential therapeutic implications of this discovery.",
  "summary": "Abstract: Endocannabinoids (eCBs) like anandamide and 2-arachidonoylglycerol are endogenous lipid ligands for CB1 and CB2 G protein-coupled receptors (GPCRs). Here, we show that phosphorylation of biologically important anandamide generates naturally occurring anandamide phosphate (AEAp), which switches GPCR ligand specificity to lysophosphatidic acid (LPA) receptors (LPARs) and the…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}