Activity of Pramlintide, Rat and Human Amylin but not Aβ_1–42 at Human Amylin Receptors

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 (Aβ_1–42) has recently been proposed to be a specific agonist of the AMY₃ receptor. We investigated the actions of Aβ_1–42 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 Aβ_1–42 at any receptor, suggesting that it may not be a genuine agonist of AMY receptors.