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Linking medicinal cannabis to autotaxin–lysophosphatidic acid signaling
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 pathophysio...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Life Science Alliance LLC
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9834664/ https://www.ncbi.nlm.nih.gov/pubmed/36623871 http://dx.doi.org/10.26508/lsa.202201595 |
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author | Eymery, Mathias C McCarthy, Andrew A Hausmann, Jens |
author_facet | Eymery, Mathias C McCarthy, Andrew A Hausmann, Jens |
author_sort | Eymery, Mathias C |
collection | PubMed |
description | 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 Δ(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)-Δ6a,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. |
format | Online Article Text |
id | pubmed-9834664 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Life Science Alliance LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-98346642023-01-13 Linking medicinal cannabis to autotaxin–lysophosphatidic acid signaling Eymery, Mathias C McCarthy, Andrew A Hausmann, Jens Life Sci Alliance Research Articles 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 Δ(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)-Δ6a,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. Life Science Alliance LLC 2023-01-09 /pmc/articles/PMC9834664/ /pubmed/36623871 http://dx.doi.org/10.26508/lsa.202201595 Text en © 2023 Eymery et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Articles Eymery, Mathias C McCarthy, Andrew A Hausmann, Jens Linking medicinal cannabis to autotaxin–lysophosphatidic acid signaling |
title | Linking medicinal cannabis to autotaxin–lysophosphatidic acid signaling |
title_full | Linking medicinal cannabis to autotaxin–lysophosphatidic acid signaling |
title_fullStr | Linking medicinal cannabis to autotaxin–lysophosphatidic acid signaling |
title_full_unstemmed | Linking medicinal cannabis to autotaxin–lysophosphatidic acid signaling |
title_short | Linking medicinal cannabis to autotaxin–lysophosphatidic acid signaling |
title_sort | linking medicinal cannabis to autotaxin–lysophosphatidic acid signaling |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9834664/ https://www.ncbi.nlm.nih.gov/pubmed/36623871 http://dx.doi.org/10.26508/lsa.202201595 |
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