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

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)....

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Bibliographic Details
Published in:Endocrinology (Philadelphia) 1996-09, Vol.137 (9), p.3674-3680
Main Authors: Crespel, A, De Boisvilliers, F, Gros, L, Kervran, A
Format: Article
Language:English
Subjects:
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
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Summary: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.
ISSN:0013-7227
1945-7170
DOI:10.1210/en.137.9.3674