title: Expression of the rat adrenomedullin receptor or a putative human adrenomedullin receptor does not correlate with adrenomedullin binding or functional response.
abstract: There has been considerable difficulty in defining distinct adrenomedullin (AM) binding sites and function in vivo. However, a rat adrenomedullin receptor (rAMR) and a putative human adrenomedullin receptor (hAMR) have recently been reported. We attempted to confirm and extend the pharmacological characterization of these cloned receptors. COS-7 cells transfected with rAMR or epitope tagged rAMR display abundant rAMR mRNA expression and cell-surface receptor localization. Specific 125I-AM binding is detected in transfected cells; however, similar levels of binding are also detected in cells transfected with vector DNA alone. This AM binding site fails to mediate any changes in cAMP in response to AM. In contrast, Swiss 3T3 cells, expressing specific endogenous AM receptors, display AM binding and functional cAMP responses. Transfection studies performed with the putative hAMR yield similar results. These data suggest that the proposed rAMR and hAMR do not represent authentic adrenomedullin receptors.
authors.affiliation: Department of Molecular Sciences, Pfizer Inc., Groton, Connecticut 06340, USA. Scott_P_Kennedy@Groton.Pfizer.Com
authors.forename: S P
authors.initials: SP
authors.lastname: Kennedy
authors.forename: D
authors.initials: D
authors.lastname: Sun
authors.forename: J J
authors.initials: JJ
authors.lastname: Oleynek
authors.forename: C F
authors.initials: CF
authors.lastname: Hoth
authors.forename: J
authors.initials: J
authors.lastname: Kong
authors.forename: R J
authors.initials: RJ
authors.lastname: Hill
mesh_terms: D016475:3T3 Cells; D053607:Adrenomedullin; D000818:Animals; D016477:Artifacts; D001667:Binding, Competitive; D019556:COS Cells; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000032:analysis; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D010455:Peptides / Q000378:metabolism*; D051381:Rats; D058265:Receptors, Adrenomedullin; D018000:Receptors, Peptide; D011994:Recombinant Proteins / Q000096:biosynthesis; D014162:Transfection
chemical_list: D008565:Membrane Proteins; D010455:Peptides; D058265:Receptors, Adrenomedullin; D018000:Receptors, Peptide; D011994:Recombinant Proteins; D053607:Adrenomedullin; D000242:Cyclic AMP