title: Activity of pramlintide, rat and human amylin but not Aβ1-42 at human amylin receptors.
abstract: 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.
authors.affiliation: 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.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Gingell
authors.forename: Erica R
authors.initials: ER
authors.lastname: Burns
authors.forename: Debbie L
authors.initials: DL
authors.lastname: Hay
mesh_terms: D000595:Amino Acid Sequence; D065091:Amylin Receptor Agonists; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002116:Calcitonin / Q000378:metabolism; D002522:Chlorocebus aethiops; D057809:HEK293 Cells; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry*; D058228:Islet Amyloid Polypeptide / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism*; D010641:Phenotype; D051381:Rats; D018003:Receptors, Calcitonin / Q000819:agonists / Q000378:metabolism; D058287:Receptors, Islet Amyloid Polypeptide / Q000378:metabolism*
chemical_list: D065091:Amylin Receptor Agonists; D016229:Amyloid beta-Peptides; D007004:Hypoglycemic Agents; D058228:Islet Amyloid Polypeptide; D010446:Peptide Fragments; D018003:Receptors, Calcitonin; D058287:Receptors, Islet Amyloid Polypeptide; C075222:amyloid beta-protein (1-42); D002116:Calcitonin; C105254:pramlintide