A phytocannabinoid-sensitive phosphorylation switch converts endocannabinoids into alternative lipid GPCR activators. (PubMed, bioRxiv) - Oct 2, 2026 - "Endocannabinoids (eCBs) like anandamide and 2-arachidonoylglycerol are endogenous lipid ligands for CB 1 and CB 2 G protein-coupled receptors (GPCRs)...DGKQ showed noncanonical biphasic lipid kinetics and was inhibited by phytocannabinoids, most notably tetrahydrocannabinolic acid. Thus, eCBs are not only cannabinoid receptor ligands but also enzymatically adaptable lipid signals activating LPARs and MRGPRX4, thus linking metabolism of the distinct lipid LPA with Cannabis pharmacology."
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Anna C Love; Bradley S Moore; David Coronel; Douglas J Sheffler; Hirotaka Mizuno; Jerold Chun; Kazufumi Nagai; Valerie P Tan; Yasuyuki Kihara
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