Identification of an orphan receptor gene as a type 1 calcitonin gene-related peptide receptor.

Calcitonin gene-related peptide (CGRP) is a 37 residue neuropeptide that is distantly related to adrenomedullin. We have recently reported the cloning and expression of an adrenomedullin receptor which is approximately 30% homologous to the canine orphan receptor RDC-1. Therefore we tested the hypothesis that RDC-1 was a CGRP receptor. The RDC-1 gene was expressed in COS-7 cells and showed a dose dependant increase of cAMP in response to CGRP and adrenomedullin (EC50 values of 3 x 10(-9) M and 1 x 10(-7) M respectively) which was inhibited by the CGRP antagonist CGRP[8-37]. There was no cAMP response to amylin or [Cys(acm)2,7]a-hCGRP. Ligand binding studies confirmed high affinity of this receptor for CGRP and CGRP[8-37] with KD values of 9.2 x 10(-9) M and 13.4 x 10(-9) M respectively.