Linking medicinal cannabis to autotaxin–lysophosphatidic acid signaling

Mathias C Eymery; Andrew A McCarthy; Jens Hausmann

doi:10.26508/lsa.202201595

journal article Open Access Jan 09, 2023

Linking medicinal cannabis to autotaxin–lysophosphatidic acid signaling

Mathias C Eymery

Andrew A McCarthy

Jens Hausmann

Life Science Alliance Vol. 6 No. 2 pp. e202201595 · Life Science Alliance, LLC

View at Publisher Save 10.26508/lsa.202201595

Abstract

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 (LPA1–6). The ATX-LPA signaling axis is a critical component in many physiological and pathophysiological conditions. Here, we describe a potent inhibition of Δ9-trans-tetrahydrocannabinol (THC), the main psychoactive compound of medicinal cannabis and related cannabinoids, on the catalysis of two isoforms of ATX with nanomolar apparent EC50values. Furthermore, we decipher the binding interface of ATX to THC, and its derivative 9(R)-Δ6a,10a-THC (6a10aTHC), by X-ray crystallography. Cellular experiments confirm this inhibitory effect, revealing a significant reduction of internalized LPA1in 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.

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Details

Published: Jan 09, 2023
Vol/Issue: 6(2)
Pages: e202201595
License: View

Authors

M

Mathias C Eymery

European Molecular Biology Laboratory, Grenoble, Grenoble, France

A

Andrew A McCarthy

European Molecular Biology Laboratory, Grenoble, Grenoble, France

J

Jens Hausmann

European Molecular Biology Laboratory, Grenoble, Grenoble, France; European Molecular Biology Laboratory, Chemical Biology Core Facility, Heidelberg, Germany

Funding

EMBL

Cite This Article

Mathias C Eymery, Andrew A McCarthy, Jens Hausmann (2023). Linking medicinal cannabis to autotaxin–lysophosphatidic acid signaling. Life Science Alliance, 6(2), e202201595. https://doi.org/10.26508/lsa.202201595

Linking medicinal cannabis to autotaxin–lysophosphatidic acid signaling

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