7p4j

Publication Abstract from PubMed

Autotaxin is primarily known for the formation of lysophosphatidic acid (LPA) from lysophosphatidylcholine. LPA is an important signaling phospholipid that can bind to six G protein-coupled receptors (LPA(1-6)). The ATX-LPA signaling axis is a critical component in many physiological and pathophysiological conditions. Here, we describe a potent inhibition of Delta(9)-trans-tetrahydrocannabinol (THC), the main psychoactive compound of medicinal cannabis and related cannabinoids, on the catalysis of two isoforms of ATX with nanomolar apparent EC(50) values. Furthermore, we decipher the binding interface of ATX to THC, and its derivative 9(R)-Delta6a,10a-THC (6a10aTHC), by X-ray crystallography. Cellular experiments confirm this inhibitory effect, revealing a significant reduction of internalized LPA(1) in the presence of THC with simultaneous ATX and lysophosphatidylcholine stimulation. Our results establish a functional interaction of THC with autotaxin-LPA signaling and highlight novel aspects of medicinal cannabis therapy.

Linking medicinal cannabis to autotaxin-lysophosphatidic acid signaling.,Eymery MC, McCarthy AA, Hausmann J Life Sci Alliance. 2023 Jan 9;6(2):e202201595. doi: 10.26508/lsa.202201595. Print , 2023 Feb. PMID:36623871^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.