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

Biochem Biophys Res Commun. 1995 Dec 26;217(3):832-8. doi: 10.1006/bbrc.1995.2847.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Adrenomedullin
  • Animals
  • Base Sequence
  • Calcitonin Gene-Related Peptide / metabolism*
  • Cells, Cultured
  • Chlorocebus aethiops
  • Cyclic AMP / metabolism
  • DNA Primers / chemistry
  • DNA, Complementary / genetics
  • Dogs
  • Gene Expression
  • Membrane Proteins / metabolism
  • Molecular Sequence Data
  • Peptides / metabolism
  • RNA, Messenger / genetics
  • Rats
  • Receptors, Adrenomedullin
  • Receptors, Calcitonin Gene-Related Peptide / genetics*
  • Receptors, Calcitonin Gene-Related Peptide / metabolism
  • Receptors, Cell Surface / metabolism*
  • Receptors, Peptide*
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Transfection

Substances

  • DNA Primers
  • DNA, Complementary
  • Membrane Proteins
  • Peptides
  • RNA, Messenger
  • Receptors, Adrenomedullin
  • Receptors, Calcitonin Gene-Related Peptide
  • Receptors, Cell Surface
  • Receptors, Peptide
  • Adrenomedullin
  • Cyclic AMP
  • Calcitonin Gene-Related Peptide