School of Biological Sciences (J.J.G., E.R.B., D.L.H.), The University of Auckland and Maurice Wilkins Centre (J.J.G., D.L.H.), University of Auckland, Auckland 1142, New Zealand.
Endocrinology. 2014 Jan;155(1):21-6. doi: 10.1210/en.2013-1658. Epub 2013 Dec 20.
Amylin is a neuroendocrine hormone involved in glucose regulation. An amylin analog, pramlintide, is used to treat insulin-requiring diabetes. Its anorexigenic actions give it potential as an obesity treatment. There are 3 amylin receptors (AMY1, AMY2, AMY3), comprising the calcitonin receptor and receptor activity-modifying proteins 1, 2, and 3, respectively. The pharmacology of pramlintide at each subtype has not been determined whereas the unrelated peptide β-amyloid 1-42 (Aβ1-42) has recently been proposed to be a specific agonist of the AMY3 receptor. We investigated the actions of Aβ1-42 and pramlintide, compared with human and rat amylin at the calcitonin receptor, AMY1, AMY2, and AMY3 receptors, measuring the cAMP response in human embryonic kidney 293S and Cos 7 cells. Pramlintide activated all receptors with a slight preference for AMY1. No cAMP response was detected with Aβ1-42 at any receptor, suggesting that it may not be a genuine agonist of AMY receptors.
胰岛淀粉样多肽是一种参与葡萄糖调节的神经内分泌激素。胰岛淀粉样多肽类似物普兰林肽被用于治疗需要胰岛素的糖尿病。其抑制食欲的作用使其有作为肥胖治疗药物的潜力。存在 3 种胰岛淀粉样多肽受体（AMY1、AMY2、AMY3），分别由降钙素受体和受体活性修饰蛋白 1、2 和 3 组成。普兰林肽在每种亚型的药理学尚未确定，而不相关的肽β-淀粉样蛋白 1-42（Aβ1-42）最近被提议为 AMY3 受体的特异性激动剂。我们研究了 Aβ1-42 和普兰林肽在降钙素受体、AMY1、AMY2 和 AMY3 受体上与人及大鼠胰岛淀粉样多肽的作用，用人胚肾 293S 和 Cos 7 细胞测量 cAMP 反应。普兰林肽对所有受体均有激活作用，对 AMY1 略有偏好。在任何受体上均未检测到 Aβ1-42 的 cAMP 反应，提示其可能不是 AMY 受体的真正激动剂。
