Extracellular calcium sensing receptor in human pancreatic cells
- 1Institute of Experimental Medicine, Hungarian Academy of Sciences, H-1083 Budapest, Hungary
- 2School of Biological Sciences, University of Manchester, Manchester M13 9PT, UK
- Correspondence to:
Dr AC Elliot, School of Biological Sciences (G38), University of Manchester, Manchester M13 9PT, UK;
and Dr G Varga, Institute of Experimental Medicine, H-1450 Budapest, PO Box 67, Hungary;
- Accepted 28 March 2002
Background and aims: The extracellular calcium sensing receptor (CaR) plays a key role in the calcium homeostatic system and is therefore widely expressed in tissues involved in calcium metabolism. However, the CaR has also been identified in other tissues where its role is less clear. We have investigated the presence of the CaR in the human pancreas.
Methods: Messenger RNA for the CaR was detected by reverse transcription-polymerase chain reaction and the protein was localised by immunostaining. CaR function was assayed in Capan-1 cells by measuring intracellular calcium and [3H] thymidine incorporation.
Results: The receptor was highly expressed in human pancreatic ducts. It was also expressed in exocrine acinar cells, in islets of Langerhans, and in intrapancreatic nerves and blood vessels. The CaR was expressed in both normal and neoplastic human tissue samples but was detected in only one of five ductal adenocarcinoma cells lines examined. Experiments on the CaR expressing adenocarcinoma cell line Capan-1 showed that the CaR was functional and was linked to mobilisation of intracellular calcium. Stimulation of the CaR reduced Capan-1 cell proliferation.
Conclusions: We propose that the CaR may play multiple functional roles in the human pancreas. In particular, the CaR on the duct luminal membrane may monitor and regulate the Ca2+ concentration in pancreatic juice by triggering ductal electrolyte and fluid secretion. This could help to prevent precipitation of calcium salts in the duct lumen. The CaR may also help to regulate the proliferation of pancreatic ductal cells.
- extracellular calcium sensing receptor
- pancreatic duct
- pancreatic ductal adenocarcinoma
- human pancreatic cell line
- CaR, calcium sensing receptor
- RT-PCR, reverse transcription-polymerase chain reaction
- PBS, phosphate buffered saline
- [Ca2+]i, intracellular free calcium ion concentration
- DAB, diaminobenzidine
- ORF, open reading frame
- HBSS, Hepes buffered salt solution