Expression of the calcium-sensing receptor in pancreatic islet B-cells

Exposure of pancreatic islet B-cells to D-glucose and many other insulinotr opic agents results in an increase of cytoplasmic calcium concentration, wh ich triggers the exocytosis of secretroy granules. Previous studies have de monstrated that calcium itself, at concentrations ranging from 2 to 18 mM, is able to induce a dose-related stimulation of insulin secretion, even in the absence of any other secretagogue. It was recently demonstrated that pa rathyroid cells and several other cell types, whether involved or not in ca lcium homeostasis, sense extracellular calcium through a G-protein coupled calcium-sensing receptor (CaSR). In the present study, the presence of the receptor in islet pancreatic B-cells was scrutinized. Using reverse transcr iptase-polymerase chain reaction and Northern blot analysis, we demonstrate the expression of the CaSR in purified rat pancreatic islet B-cells. The n ucleotide sequences of the rt-PCR products demonstrated more than 99% homol ogy with the rat kidney CaSR complementary DNA. A specific 5.3 kb transcrip t of the CaSR was expressed in normal pancreatic B-cells as well as in tumo ral insulin-secreting cells. In pancreatic islets, the physiological role o f the CaSR in the regulation of insulin release could involve the sensing o f endogenous ligands other than calcium. (C) 1999 Academic Press.