Kotańska Magdalena, Mika Kamil, Szafarz Małgorzata, Kubacka Monika, Müller Christa E, Sapa Jacek, Kieć-Kononowicz Katarzyna
Department of Pharmacological Screening, Faculty of Pharmacy, Jagiellonian University, Medical College, 9 Medyczna Street, 30-688 Kraków, Poland.
Department of Pharmacokinetics and Physical Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688, Krakow, Poland.
Pharmaceuticals (Basel). 2021 Mar 16;14(3):270. doi: 10.3390/ph14030270.
GPR18 has been proposed to play a role in the progression of metabolic disease and obesity. Therefore, the aim of this study was to determine the effects of selective GRP18 ligands (the antagonists PSB-CB5 and PSB-CB27 and the agonist PSB-KK1415) on body mass and the development of metabolic disorders commonly accompanying obesity. Experiments were carried out on female Wistar rats. In order to determine the anorectic activity of the investigated ligands, their effect on food and water intake in a model of excessive eating was assessed. Lipid profile, glucose and insulin levels as well as alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transpeptidase activity in plasma were also evaluated. Potential side effects were examined in rat models of pica behavior and conditioned taste aversion. Animals treated with different ligands gained significantly less weight than rats from the obese control group. Effects of GPR18 antagonists on food intake and body weight were specific and unrelated to visceral illness, stress or changes in spontaneous activity. However, the GPR18 agonist is likely to affect body weight by inducing gastrointestinal disorders such as nausea. The presented preliminary data support the idea that the search for selective GPR18 antagonists for the treatment of obesity might be promising.
GPR18被认为在代谢性疾病和肥胖的进展中起作用。因此，本研究的目的是确定选择性GRP18配体（拮抗剂PSB-CB5和PSB-CB27以及激动剂PSB-KK1415）对体重以及肥胖常见伴随的代谢紊乱发展的影响。实验在雌性Wistar大鼠身上进行。为了确定所研究配体的厌食活性，评估了它们在暴饮暴食模型中对食物和水摄入的影响。还评估了血脂谱、血糖和胰岛素水平以及血浆中的丙氨酸转氨酶、天冬氨酸转氨酶和γ-谷氨酰转肽酶活性。在异食癖行为和条件性味觉厌恶的大鼠模型中检查了潜在的副作用。用不同配体处理的动物体重增加明显少于肥胖对照组的大鼠。GPR18拮抗剂对食物摄入和体重的影响是特异性的，与内脏疾病、应激或自发活动变化无关。然而，GPR18激动剂可能通过诱发恶心等胃肠道疾病来影响体重。所呈现的初步数据支持这样一种观点，即寻找用于治疗肥胖的选择性GPR18拮抗剂可能是有前景的。
