Cys2,7EtalphaCGRP is a potent agonist for CGRP1 receptors in SK-N-MC cells

Biochem Pharmacol. 2005 Apr 15;69(8):1235-40. doi: 10.1016/j.bcp.2005.01.008.


The present study reveals that cystein2,7 ethyl-amidealphaCGRP (Cys2,7EtalphaCGRP), an advertised calcitonin gene-related peptide 2 (CGRP2) receptor subtype-selective agonist, is also a potent agonist for the calcitonin gene-related peptide 1 (CGRP1) receptors natively expressed in the SK-N-MC human neuroblastoma cell line. Cys2,7EtalphaCGRP and alpha calcitonin gene-related peptide (alphaCGRP) promote cyclic AMP accumulation in intact SK-N-MC cells to the same extent with EC50 of 1.6+/-0.2 and 0.4+/-0.08 nM, respectively. The antagonist alpha calcitonin gene-related peptide-8-37 (alphaCGRP-(8-37)) produces a concentration-dependent rightward shift of the alphaCGRP- and Cys2,7EtalphaCGRP concentration-response curves with KB-values (71+/-33 and 47+/-21 nM, respectively). The competitive antagonism by alphaCGRP-(8-37) and the similar KB-values suggests that alphaCGRP and Cys2,7EtalphaCGRP stimulate the same receptor. In competition binding studies with [125I]-alphaCGRP on SK-N-MC cell membranes, Cys2,7EtalphaCGRP and alphaCGRP-(8-37) display high affinity for the majority of the binding sites with Ki-values of 0.030+/-0.013 and 0.60+/-0.013 nM, respectively. The present findings are at odds with the proclaimed utilization of Cys2,7EtalphaCGRP as a CGRP2 receptor-selective pharmacological tool. Differences between the agonistic profile of this ligand in this and other experimental systems might be species--or even cell type--dependent.

Publication types

  • Comparative Study

MeSH terms

  • Binding Sites
  • Binding, Competitive
  • Calcitonin Gene-Related Peptide / pharmacology*
  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • Cyclic AMP / biosynthesis
  • Dose-Response Relationship, Drug
  • Humans
  • Iodine Radioisotopes
  • Kinetics
  • Ligands
  • Neuroblastoma / metabolism*
  • Peptide Fragments / pharmacology*
  • Receptors, Calcitonin Gene-Related Peptide / agonists*
  • Receptors, Calcitonin Gene-Related Peptide / metabolism


  • Iodine Radioisotopes
  • Ligands
  • Peptide Fragments
  • Receptors, Calcitonin Gene-Related Peptide
  • calcitonin gene-related peptide (8-37)
  • Cyclic AMP
  • Calcitonin Gene-Related Peptide