Pharmacology of the human CGRP1 receptor in Cos 7 cells

Only limited pharmacological characterization of the CGRP1 receptor, a heterodimer of the calcitonin (CT) receptor-like receptor (CL) and receptor activity-modifying protein 1 has been performed in cells that do not endogenously express RAMP2. We characterized the receptor in RAMP-deficient Cos 7 cells by measuring cAMP responses following agonist treatment in the absence or presence of antagonists. Potent cAMP responses to human α-and β-CGRP (Cys(Et)2,7)hαCGRP and human adrenomedullin (AM) were observed. Adrenomedullin15–52 was also an effective agonist of the CGRP1 receptor but human and salmon calcitonin and rat amylin were only weak agonists. As expected, BIBN4096BS and CGRP8–37 were effective antagonists of the CGRP1 receptor. (Cys(Acm)2,7)hαCGRP also antagonized CGRP responses. Antagonists of related receptors were only weakly able to inhibit CGRP responses.