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

Gastroenterology. 2001 Apr;120(5):1128-39. doi: 10.1053/gast.2001.23246.


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 A(2), 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / pharmacology
  • Caffeine / pharmacology
  • Calcium / pharmacology
  • Calcium Channel Blockers / pharmacology
  • Cells, Cultured
  • Cyclic AMP / metabolism
  • DNA Primers
  • Enzyme Inhibitors / pharmacology
  • Gastric Mucosa / enzymology
  • Gastrins / metabolism
  • Gene Expression / physiology
  • Humans
  • Indoles / pharmacology
  • Maleimides / pharmacology
  • Nitrendipine / pharmacology
  • Phosphodiesterase Inhibitors / pharmacology
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism
  • Pyloric Antrum / cytology*
  • Pyloric Antrum / metabolism*
  • RNA, Messenger / analysis
  • Receptors, Calcium-Sensing
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • ortho-Aminobenzoates / pharmacology


  • Calcium Channel Blockers
  • DNA Primers
  • Enzyme Inhibitors
  • Gastrins
  • Indoles
  • Maleimides
  • Phosphodiesterase Inhibitors
  • RNA, Messenger
  • Receptors, Calcium-Sensing
  • Receptors, Cell Surface
  • ortho-Aminobenzoates
  • 9-(tetrahydro-2-furyl)-adenine
  • Caffeine
  • fenamic acid
  • Nitrendipine
  • Cyclic AMP
  • Protein Kinase C
  • Adenine
  • bisindolylmaleimide I
  • Calcium