Evidence for calcitonin receptor heterogeneity: binding studies with nonhelical analogs

Endocrinology. 1990 Jul;127(1):163-9. doi: 10.1210/endo-127-1-163.


Binding of the nonhelical salmon calcitonin (sCT) analog, [Gly8,Ala16]-des-Leu19-sCT to membrane preparations from rat brain could be analyzed in terms of two independent binding sites. The high and low affinity binding sites for this analog were named CT-L (L, linear) and CT-H (H, helix), respectively. Although the CT-H type receptor has a low affinity for the nonhelical analogs, it binds the helical sCT with high affinity and therefore represents a CT binding site. The physiological significance for the existence of subtypes of specific CT receptors is not clear. The [Gly8,Ala16]-des-Leu19-sCT suppressed the osteoclastic bone resorption in tissue culture at low concentration (0.1 nM). The dose of [Gly8,Ala16]-des-Leu19-sCT required for this hypocalcemic activity was highly correlated with the binding affinity of this analog to the CT-L receptor subtype. In addition, human CT interacted with the CT-L type receptor at about 100th the concentration of that required for the displacement of sCT. We conclude that binding to the CT-L type receptor is required for hypocalcemic activity in mammals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Binding, Competitive
  • Bone Resorption
  • Brain / metabolism
  • Calcitonin / analogs & derivatives*
  • Calcitonin / metabolism*
  • Calcitonin / pharmacology
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Kidney / metabolism
  • Male
  • Osteoclasts / physiology
  • Osteoclasts / ultrastructure
  • Protein Conformation
  • Rats
  • Rats, Inbred Strains
  • Receptors, Calcitonin
  • Receptors, Cell Surface / metabolism*


  • Receptors, Calcitonin
  • Receptors, Cell Surface
  • calcitonin, salmon, Gly(8)-Ala(16)-des-Leu(19)-
  • salmon calcitonin
  • Calcitonin