Department of Pharmacology, Faculty of Medicine, Kahramanmaras Sutcu Imam University, Avşar Kampusu, Onikişubat, Kahramanmaraş, Turkey.
Department of Pharmacology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey.
Psychopharmacology (Berl). 2019 Jun;236(6):1717-1728. doi: 10.1007/s00213-018-5154-7. Epub 2019 Jan 4.
Glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) are gut derived hormones. GLP-1 and GLP-2 were shown to have pleiotropic effects in intestinal and pancreatic diseases.
We aimed to investigate the activities of GLP-1 and GLP-2 on nociception and inflammation in mice, involving their actions on serotonergic, nitrergic, and opioidergic systems.
Antinociceptive and anti-inflammatory activities of intraperitoneally injected GLPs were evaluated in hotplate latency test, formalin-induced behavioral, and paw edema tests. Ondansetron, a selective 5-HT receptor antagonist; L-NAME, a NOS inhibitor; and naloxone, an opioid antagonist were injected to determine the mechanisms of antinociception and anti-inflammation. We also measured blood glucose levels and performed rotarod test in order to evaluate whether the hypoglycemic effect of GLP compounds or alterations in locomotor activity may affect the latency in hotplate test and activity in formalin test.
GLP-1 (0.2 mg/kg) and GLP-2 (0.05, 0.2 mg/kg) significantly increased pain threshold. GLP-1 (0.2 mg/kg) and GLP-2 (0.05, 0.1, 0.2 mg/kg) significantly decreased formalin-induced licking and shaking behaviors. GLP-1 or GLP-2 showed no significant inhibitory action on formalin-induced swelling in paws of mice. Antinociceptive actions of GLP-1 and GLP-2 were significantly decreased with ondansetron and naloxone, and paw shaking behavior significantly increased with naloxone. GLP-1 and GLP-2 did not impair rotarod performance, and did not cause a significant hypoglycemic effect in our normoglycemic mice after rotarod test.
These finding indicated that the antinociceptive and anti-inflammatory effect of GLP-1 was related to opioidergic system. Antinociceptive effect of GLP-2 was partially related to 5-HT3 serotonergic or opioidergic system in hotplate test. However, the anti-inflammatory effect of GLP-2 was not directly related to 5-HT3, NO or opioids.
胰高血糖素样肽-1（GLP-1）和胰高血糖素样肽-2（GLP-2）是肠道衍生的激素。GLP-1 和 GLP-2 已被证明在肠道和胰腺疾病中有多种作用。
我们旨在研究 GLP-1 和 GLP-2 对小鼠痛觉和炎症的作用，包括它们对 5-羟色胺能、硝化能和阿片能系统的作用。
通过热板潜伏期试验、福尔马林诱导的行为和爪肿胀试验评估腹腔注射 GLP 的抗伤害和抗炎活性。奥丹赛酮，一种选择性 5-HT 受体拮抗剂；L-NAME，一种 NOS 抑制剂；纳洛酮，一种阿片受体拮抗剂，用于确定抗伤害和抗炎的机制。我们还测量了血糖水平，并进行了旋转棒试验，以评估 GLP 化合物的降血糖作用或运动活动的改变是否会影响热板试验中的潜伏期和福尔马林试验中的活动。
GLP-1（0.2mg/kg）和 GLP-2（0.05、0.2mg/kg）显著提高了痛觉阈值。GLP-1（0.2mg/kg）和 GLP-2（0.05、0.1、0.2mg/kg）显著减少了福尔马林诱导的舔舐和抖动行为。GLP-1 或 GLP-2 对小鼠爪子的福尔马林诱导肿胀没有明显的抑制作用。GLP-1 和 GLP-2 的抗伤害作用随着奥丹赛酮和纳洛酮的使用而显著降低，而纳洛酮则显著增加了爪子的抖动行为。GLP-1 和 GLP-2 不会损害旋转棒的性能，并且在我们的正常血糖小鼠进行旋转棒试验后，也不会导致明显的低血糖作用。
这些发现表明，GLP-1 的镇痛和抗炎作用与阿片能系统有关。热板试验中，GLP-2 的镇痛作用部分与 5-HT3 5-羟色胺能或阿片能系统有关。然而，GLP-2 的抗炎作用与 5-HT3、NO 或阿片类药物没有直接关系。
