Characterization of the Synergistic Effect between Ligands of Opioid and Free Fatty Acid Receptors in the Mouse Model of Colitis
Background: Recent studies suggest that lipids, including free fatty acids (FFAs), are necessary for proper μ opioid receptor (MOR) binding and that activation of opioid receptors (ORs) improves intestinal inflammation. The objective of the study was to investigate a possible interaction between the...
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2021
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oai:doaj.org-article:dec6719a244a4da589acc3de5e7f73702021-11-25T18:27:33ZCharacterization of the Synergistic Effect between Ligands of Opioid and Free Fatty Acid Receptors in the Mouse Model of Colitis10.3390/molecules262268271420-3049https://doaj.org/article/dec6719a244a4da589acc3de5e7f73702021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/22/6827https://doaj.org/toc/1420-3049Background: Recent studies suggest that lipids, including free fatty acids (FFAs), are necessary for proper μ opioid receptor (MOR) binding and that activation of opioid receptors (ORs) improves intestinal inflammation. The objective of the study was to investigate a possible interaction between the ORs and FFA receptors (FFARs) ligands in the colitis. Methods: The potential synergistic effect of ORs and FFARs ligands was evaluated using mouse model of acute colitis induced by dextran sulfate sodium (DSS, 4%). Compounds were injected intraperitoneally (i.p.) once or twice daily at the doses of 0.01 or 0.02 mg/kg body weight (BW) (DAMGO—an MOR agonist), 0.3 mg/kg BW (DPDPE—a δ OR (DOR) agonist) and 1 mg/kg BW (naloxone—a non-selective OR antagonist, GLPG 0974—a FFAR2 antagonist, GSK 137647—a FFAR4 agonist and AH 7614—a FFAR4 antagonist) for 4 days. Results: Myeloperoxidase (MPO) activity was significantly decreased after DAMGO (0.02 mg/kg BW) and GSK 137647 (1 mg/kg BW) administration and co-administration as compared to DSS group. Conclusions: Treatment with ligands of ORs and FFARs may affect the immune cells in the inflammation; however, no significant influence on the severity of colitis and no synergistic effect were observed.Agata BiniendaAdam MakaroMarcin TalarJulia B. KrajewskaAleksandra TarasiukAdrian BartoszekAdam FabisiakPaula MosińskaKarolina NiewinnaKatarzyna DziedziczakMikołaj ŚwierczyńskiRadzisław KordekMaciej SalagaJakub FichnaMDPI AGarticlefree fatty acid receptorslipidsopioid receptorDAMGOcolitisOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6827, p 6827 (2021) |
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| topic |
free fatty acid receptors lipids opioid receptor DAMGO colitis Organic chemistry QD241-441 |
| spellingShingle |
free fatty acid receptors lipids opioid receptor DAMGO colitis Organic chemistry QD241-441 Agata Binienda Adam Makaro Marcin Talar Julia B. Krajewska Aleksandra Tarasiuk Adrian Bartoszek Adam Fabisiak Paula Mosińska Karolina Niewinna Katarzyna Dziedziczak Mikołaj Świerczyński Radzisław Kordek Maciej Salaga Jakub Fichna Characterization of the Synergistic Effect between Ligands of Opioid and Free Fatty Acid Receptors in the Mouse Model of Colitis |
| description |
Background: Recent studies suggest that lipids, including free fatty acids (FFAs), are necessary for proper μ opioid receptor (MOR) binding and that activation of opioid receptors (ORs) improves intestinal inflammation. The objective of the study was to investigate a possible interaction between the ORs and FFA receptors (FFARs) ligands in the colitis. Methods: The potential synergistic effect of ORs and FFARs ligands was evaluated using mouse model of acute colitis induced by dextran sulfate sodium (DSS, 4%). Compounds were injected intraperitoneally (i.p.) once or twice daily at the doses of 0.01 or 0.02 mg/kg body weight (BW) (DAMGO—an MOR agonist), 0.3 mg/kg BW (DPDPE—a δ OR (DOR) agonist) and 1 mg/kg BW (naloxone—a non-selective OR antagonist, GLPG 0974—a FFAR2 antagonist, GSK 137647—a FFAR4 agonist and AH 7614—a FFAR4 antagonist) for 4 days. Results: Myeloperoxidase (MPO) activity was significantly decreased after DAMGO (0.02 mg/kg BW) and GSK 137647 (1 mg/kg BW) administration and co-administration as compared to DSS group. Conclusions: Treatment with ligands of ORs and FFARs may affect the immune cells in the inflammation; however, no significant influence on the severity of colitis and no synergistic effect were observed. |
| format |
article |
| author |
Agata Binienda Adam Makaro Marcin Talar Julia B. Krajewska Aleksandra Tarasiuk Adrian Bartoszek Adam Fabisiak Paula Mosińska Karolina Niewinna Katarzyna Dziedziczak Mikołaj Świerczyński Radzisław Kordek Maciej Salaga Jakub Fichna |
| author_facet |
Agata Binienda Adam Makaro Marcin Talar Julia B. Krajewska Aleksandra Tarasiuk Adrian Bartoszek Adam Fabisiak Paula Mosińska Karolina Niewinna Katarzyna Dziedziczak Mikołaj Świerczyński Radzisław Kordek Maciej Salaga Jakub Fichna |
| author_sort |
Agata Binienda |
| title |
Characterization of the Synergistic Effect between Ligands of Opioid and Free Fatty Acid Receptors in the Mouse Model of Colitis |
| title_short |
Characterization of the Synergistic Effect between Ligands of Opioid and Free Fatty Acid Receptors in the Mouse Model of Colitis |
| title_full |
Characterization of the Synergistic Effect between Ligands of Opioid and Free Fatty Acid Receptors in the Mouse Model of Colitis |
| title_fullStr |
Characterization of the Synergistic Effect between Ligands of Opioid and Free Fatty Acid Receptors in the Mouse Model of Colitis |
| title_full_unstemmed |
Characterization of the Synergistic Effect between Ligands of Opioid and Free Fatty Acid Receptors in the Mouse Model of Colitis |
| title_sort |
characterization of the synergistic effect between ligands of opioid and free fatty acid receptors in the mouse model of colitis |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/dec6719a244a4da589acc3de5e7f7370 |
| work_keys_str_mv |
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| _version_ |
1718411165196877824 |