Effects of glucagon and glucagon-like peptide-1-(7-36) amide on C cells from rat thyroid and medullary thyroid carcinoma CA-77 cell line

Endocrinology. 1996 Sep;137(9):3674-80. doi: 10.1210/endo.137.9.8756532.


Glucagon is known to stimulate calcitonin secretion by thyroid C cells over a wide range of concentrations, raising the possibility of its interaction with several types of receptors. This study was designed to characterize receptors that mediate the effect of glucagon on a rat C cell line (CA-77). Binding studies, using radiolabeled [125I]glucagon and [125I]glucagon-like peptide-1-(7-36) amide ([125I]tGLP-1), to CA-77 plasma membranes demonstrated the presence of 1) a glucagon receptor with a dissociation constant (Kd) of 2.3 nM and relative potencies for structurally related peptides as follows: glucagon > oxyntomodulin > > tGLP-1; and 2) a tGLP-1 receptor with a Kd of 0.33 nM and relative potencies as follows: tGLP-1 > oxyntomodulin > glucagon. Glucagon stimulated calcitonin secretion from CA-77 cells in a dose-dependent manner over 4 orders of magnitude, with a maximal response of 312% over the basal value and an ED50 close to 50 nM. tGLP-1 induced a calcitonin release over 2 orders of magnitude, with a maximal response of 170% over the basal value and an ED50 close to 0.2 nM. Glucagon and tGLP-1 stimulated cAMP production in CA-77 cells to similar maximal levels over 4 and 2 orders of magnitude, respectively. The stimulation of cAMP production by glucagon at concentrations over 10 nM was suppressed by the tGLP-1 antagonist exendin-(9-39) amide, whereas the stimulation of calcitonin secretion was only partly abolished. Using a perifusion system of rat thyroid, glucagon and tGLP-1 stimulated calcitonin secretion in a calcium-dependent manner. It is concluded that glucagon and tGLP-1 receptors are expressed in the rat C cell line (CA-77) and in the normal rat thyroid. The effects of glucagon on calcitonin secretion observed at high concentrations are mediated in part through interaction with tGLP-1 receptors and via an additional non-cAMP-mediated mechanism.

MeSH terms

  • Animals
  • Binding, Competitive
  • Calcitonin / metabolism
  • Carcinoma, Medullary / metabolism*
  • Carcinoma, Medullary / pathology
  • Cyclic AMP / biosynthesis
  • Glucagon / metabolism
  • Glucagon / pharmacology*
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptides
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology*
  • Perfusion
  • Rats
  • Rats, Wistar
  • Thyroid Gland / cytology
  • Thyroid Gland / drug effects*
  • Thyroid Gland / metabolism
  • Thyroid Neoplasms / metabolism*
  • Thyroid Neoplasms / pathology
  • Tumor Cells, Cultured


  • Peptide Fragments
  • glucagon-like peptide 1 (7-36)amide
  • exendin (9-39)
  • Glucagon-Like Peptides
  • Glucagon-Like Peptide 1
  • Calcitonin
  • Glucagon
  • Cyclic AMP