EXPRESSION OF A CALCIUM-SENSING RECEPTOR IN A HUMAN MEDULLARY-THYROIDCARCINOMA CELL-LINE AND ITS CONTRIBUTION TO CALCITONIN SECRETION

An extracellular Ca2+-sensing mechanism consisting of a G protein-coup led receptor linked to phosphoinositide turnover and inhibition of PTH secretion, has recently been identified in bovine parathyroid cells. In C cells, voltage-dependent L-type calcium channels are thought to b e involved in calcium-sensing mechanisms, but evidence exists for addi tional calcium-sensing mechanisms, such as via a calcium-sensing recep tor (CaSR). Using the human medullary C cell carcinoma cell line TT, w hich lacks L-type calcium channels, we found that Ca2+ or cations spec ific for the CaSR lead to the release of calcium ions from intracellul ar stores and to an increase in calcitonin secretion. By molecular clo ning we isolated the complete protein-coding complementary DNA of a Ca SR from human TT cells, which are derived from a human medullary thyro id carcinoma. The CaSR is derived from the same CaSR gene expressed in the parathyroid gland. In addition, TI cells contain an alternative r eceptor form of CaSR, CaSRb. These findings provide strong evidence fo r the presence of a functional CaSR in the human C cell line TT. This receptor contributes not only to the inhibition of PTH secretion in th e parathyroid, but also to the stimulation of calcitonin secretion in C cells.