Expression of the rat adrenomedullin receptor or a putative human adrenomedullin receptor does not correlate with adrenomedullin binding or functional response

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 I-125-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. (C) 1998 Academic Press.