Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, 92-215 Lodz, Poland.
Department of Digestive Tract Diseases, Medical University of Lodz, 93-281 Lodz, Poland.
Molecules. 2021 Nov 11;26(22):6827. doi: 10.3390/molecules26226827.
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.
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.
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.
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.
最近的研究表明，脂质，包括游离脂肪酸（FFAs），对于μ阿片受体（MOR）的正确结合是必要的，而阿片受体（ORs）的激活可以改善肠道炎症。本研究的目的是研究 ORs 和 FFA 受体（FFARs）配体在结肠炎中的相互作用。
采用葡聚糖硫酸钠（DSS，4%）诱导的急性结肠炎小鼠模型评估 ORs 和 FFARs 配体的潜在协同作用。化合物以 0.01 或 0.02 mg/kg 体重（BW）（DAMGO-一种 MOR 激动剂）、0.3 mg/kg BW（DPDPE-一种 δ OR（DOR）激动剂）和 1 mg/kg BW（naloxone-一种非选择性 OR 拮抗剂，GLPG 0974-一种 FFAR2 拮抗剂，GSK 137647-一种 FFAR4 激动剂和 AH 7614-一种 FFAR4 拮抗剂）的剂量每天腹腔内（i.p.）注射一次或两次，共 4 天。
与 DSS 组相比，DAMGO（0.02 mg/kg BW）和 GSK 137647（1 mg/kg BW）给药后髓过氧化物酶（MPO）活性显著降低，且联合给药后活性进一步降低。
ORs 和 FFARs 配体的治疗可能会影响炎症中的免疫细胞，但对结肠炎的严重程度没有明显影响，也没有观察到协同作用。
