Activity of Pramlintide, Rat and Human Amylin but not Aβ1-42 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 (AMY(1), AMY(2), AMY(3)), 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 beta-amyloid 1-42 (A beta(1-42)) has recently been proposed to be a specific agonist of the AMY(3) receptor. We investigated the actions of A beta(1-42) and pramlintide, compared with human and rat amylin at the calcitonin receptor, AMY(1), AMY(2), and AMY(3) receptors, measuring the cAMP response in human embryonic kidney 293S and Cos 7 cells. Pramlintide activated all receptors with a slight preference for AMY(1). No cAMP response was detected with A beta(1-42) at any receptor, suggesting that it may not be a genuine agonist of AMY receptors.