| Autor: |
Kurz, Michael, Ulrich, Michaela, Kirchhofer, Sina B., Bittner, Alwina, Daude, Michael, Diederich, Wibke E., Pauck, Kim, Garn, Holger, Bu¨nemann, Moritz |
| Zdroj: |
Molecular Pharmacology; 2024, Vol. 106 Issue: 5 p216-224, 9p |
| Abstrakt: |
Aberrant type 2 inflammatory responses are the underlying cause of the pathophysiology of allergic asthma, allergic rhinitis, and other atopic diseases, with an alarming prevalence in relevant parts of the Western world. A bulk of evidence points out the important role of the DP2 receptor in these inflammation processes. A screening of different polyunsaturated fatty acids at a fluorescence resonance energy transfer–based DP2 receptor conformation sensor expressed in human embryonic kidney (HEK) cells revealed an agonistic effect of the prostaglandin (PG)-D2precursor arachidonic acid on DP2 receptor activity of about 80% of the effect induced by PGD2. In a combination of experiments at the conformation sensor and using a bioluminescence resonance energy transfer–based G protein activation sensor expressed together with DP2 receptor wild type in HEK cells, we found that arachidonic acid acts as a direct activator of the DP2 receptor, but not the DP1 receptor, in a concentration range considered physiologically relevant. Pharmacological inhibition of cyclooxygenases and lipoxygenases as well as cytochrome P450 did not lead to a diminished arachidonic acid response on the DP2 receptor, confirming a direct action of arachidonic acid on the receptor.SIGNIFICANCE STATEMENTThis study identified the prostaglandin precursor arachidonic acid to directly activate the DP2 receptor, a G protein–coupled receptor that is known to play an important role in type 2 inflammation. |
| Databáze: |
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