Mechanism of action of the calcium-sensing receptor in human antral gastrin cells

Buchan, Alison M. J., Squires, Paul E., Ring, Mark and Meloche, R. Mark (2001) Mechanism of action of the calcium-sensing receptor in human antral gastrin cells. Gastroenterology, 120 (5). pp. 1128-1139. ISSN 0016-5085

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Background and Aims: Human G cells express the calcium-sensing receptor and respond to extracellular calcium by releasing gastrin. However, the receptor on G cells is insensitive to serum calcium levels. We investigated whether this is a result of differential regulation of signaling pathways compared with parathyroid or calcitonin cells. Methods: Gastrin release from primary cultures of human antral epithelial cells enriched for G cells (35%) was measured by radioimmunoassay. G cells were stimulated by increasing extracellular calcium concentration for 1 hour in the presence or absence of antagonists of specific intracellular signaling pathways. Intracellular calcium levels were monitored to evaluate the effect of the antagonists on calcium influx. Results: Inhibition of phospholipase C decreased calcium-stimulated gastrin release, but blockers of adenylate cyclase, phospholipase A2, or mitogen-activated protein kinase had no effect. Inhibition of protein kinase C, nonselective cation channels, and phosphodiesterase increased basal and calcium-stimulated gastrin release while decreasing calcium influx. These data were consistent with basally active phosphodiesterase. Conclusions: The calcium-sensing receptor on the G cell activates phospholipase C and opens nonselective cation channels, resulting in an influx of extracellular calcium. Protein kinase C isozymes expressed by the G cells play multiple roles regulating both gastrin secretion and phosphodiesterase activity.

Keywords:adenylate cyclase, calcium sensing receptor, cation channel, gastrin, mitogen activated protein kinase, phosphodiesterase, phospholipase A2, phospholipase C inhibitor, protein kinase C inhibitor, amino acid sequence, article, calcium blood level, calcium cell level, calcium signaling, calcium transport, controlled study, enzyme activity, enzyme inhibition, gastrin cell, hormonal regulation, hormone release, human, human cell, nucleotide sequence, priority journal, protein expression, radioimmunoassay, sequence analysis, signal transduction, Adenine, Anthranilic Acids, Caffeine, Calcium, Calcium Channel Blockers, Cells, Cultured, Cyclic AMP, DNA Primers, Enzyme Inhibitors, Gastric Mucosa, Gastrins, Gene Expression, Humans, Indoles, Maleimides, Nitrendipine, Phosphodiesterase Inhibitors, Protein Kinase C, Pyloric Antrum, Receptors, Calcium-Sensing, Receptors, Cell Surface, RNA, Messenger, Signal Transduction
Subjects:C Biological Sciences > C990 Biological Sciences not elsewhere classified
Divisions:College of Science > School of Life Sciences
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ID Code:14331
Deposited On:13 Jun 2014 11:20

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