Emesis Research Group, Neuro-degeneration, Development and Repair, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
Neuropharmacology. 2013 Jul;70:141-7. doi: 10.1016/j.neuropharm.2013.01.013. Epub 2013 Jan 25.
The use of glucagon-like peptide-1 (7-36) amide (GLP-1) receptor agonists for the treatment of type 2 diabetes mellitus is commonly associated with nausea and vomiting. Therefore, the present studies investigated the potential of GLP-1 receptor ligands to modulate emesis and feeding in Suncus murinus. Exendin-4, a selective GLP-1 receptor agonist, was administered subcutaneously (1-30 nmol/kg) or intracerebroventricularly (0.03-3 nmol) after 12-h of fasting. In other studies, animals were pretreated with the GLP-1 receptor antagonist, exendin (9-39), or saline (5 μl) 15 min prior to exendin-4 (3 nmol, i.c.v.). Behaviour of animals and food and water intake were then recorded for 1-2 h; c-Fos expression was also assessed in the brains of animals in the i.c.v. studies. The subcutaneous administration of exendin-4 reduced food and water intake (p < 0.001) and induced emesis in 40% of animals (p > 0.05). The intracerebroventricular administration of exendin-4 also prevented feeding, and induced emesis (p < 0.01). In these studies, exendin (9-39) (30 nmol, i.c.v.) antagonised emesis induced by exendin-4 and the increased c-Fos expressions in the brainstem and hypothalamus (p < 0.05), but it was ineffective in reversing the exendin-4-induced inhibition of food and water intake (p > 0.05). These data suggest that exendin-4 exerts its emetic effects in the brainstem and/or hypothalamus via GLP-1 receptors. The action of exendin-4 to suppress feeding may involve non-classical GLP-1 receptors or other mechanisms.
胰高血糖素样肽-1（7-36）酰胺（GLP-1）受体激动剂被广泛用于治疗 2 型糖尿病，但常伴有恶心和呕吐等不良反应。因此，本研究旨在探讨 GLP-1 受体配体对沙鼠恶心和摄食行为的调节作用。外源性 GLP-1 受体选择性激动剂艾塞那肽以皮下注射（1-30 nmol/kg）或侧脑室注射（0.03-3 nmol）的方式给药，给药前动物禁食 12 小时。在另一项研究中，动物预先经腹腔注射 GLP-1 受体拮抗剂 exendin（9-39）或生理盐水（5 μl）15 分钟后，再经侧脑室注射艾塞那肽（3 nmol）。随后观察动物的行为变化，并记录 1-2 小时内的摄食和饮水情况；还通过免疫组化法检测侧脑室注射艾塞那肽后动物脑内 c-Fos 的表达情况。皮下注射艾塞那肽可显著减少动物的摄食和饮水（p < 0.001），并诱导 40%的动物发生呕吐（p > 0.05）。侧脑室注射艾塞那肽也可抑制动物的摄食行为，并诱导呕吐（p < 0.01）。在这些研究中，侧脑室预先注射 GLP-1 受体拮抗剂 exendin（9-39）（30 nmol）可拮抗艾塞那肽诱导的呕吐反应，以及脑桥和下丘脑内 c-Fos 的表达增加（p < 0.05），但不能逆转艾塞那肽对摄食和饮水的抑制作用（p > 0.05）。这些结果表明，艾塞那肽可能通过 GLP-1 受体在脑桥和/或下丘脑发挥其致吐作用。艾塞那肽抑制摄食的作用可能涉及非经典 GLP-1 受体或其他机制。
