EXPRESSION OF THE RAT ADRENOMEDULLIN RECEPTOR OR A PUTATIVE HUMAN ADRENOMEDULLIN RECEPTOR DOES NOT CORRELATE WITH ADRENOMEDULLIN BINDING ORFUNCTIONAL-RESPONSE

There has been considerable difficulty in defining distinct adrenomedu llin (AM) binding sites and function in vivo. However, a rat adrenomed ullin receptor (rAMR) and a putative human adrenomedullin receptor (hA MR) have recently been reported. We attempted to confirm and extend th e pharmacological characterization of these cloned receptors. COS-7 ce lls transfected with rAMR or epitope tagged rAMR display abundant rAMR mRNA expression and cell-surface receptor localization. Specific I-12 5-AM binding is detected in transfected cells; however, similar levels of binding are also detected in cells transfected with vector DNA alo ne. This AM binding site fails to mediate any changes in cAMP in respo nse to AM. In contrast, Swiss 3T3 cells, expressing specific endogenou s AM receptors, display AM binding and functional cAMP responses. Tran sfection studies performed with the putative hAMR yield similar result s. These data suggest that the proposed rAMR and hAMR do not represent authentic adrenomedullin receptors. (C) 1998 Academic Press.