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

A M Buchan ¹, P E Squires , M Ring

⁰Department of Physiology, Faculty of Medicine, 2146 Health Sciences Mall, University of British Columbia, Vancouver V6T 1Z3, Canada. ambuchan@interchange.ubc.ca

Gastroenterology +

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March 27, 2001

View abstract on PubMed

Summary

Human G cells release gastrin via calcium-sensing receptors. Phospholipase C activation and cation channel opening are key, with protein kinase C regulating secretion and phosphodiesterase activity.

Area Of Science

Gastroenterology
Cell Biology
Endocrinology

Background

Human G cells possess calcium-sensing receptors that trigger gastrin release in response to extracellular calcium.
The G cell receptor's insensitivity to serum calcium levels suggests unique regulatory mechanisms compared to other calcium-sensing cells.

Purpose Of The Study

To investigate the intracellular signaling pathways involved in calcium-sensing receptor regulation on human G cells.
To compare G cell signaling with that of parathyroid and calcitonin cells.

Main Methods

Gastrin release was measured using radioimmunoassay in primary human antral epithelial cell cultures.
Cells were stimulated with varying extracellular calcium concentrations, with specific intracellular signaling pathway antagonists tested.
Intracellular calcium levels were monitored to assess the impact of antagonists on calcium influx.

Main Results

Inhibition of phospholipase C reduced calcium-stimulated gastrin release.
Blockers of adenylate cyclase, phospholipase A2, or mitogen-activated protein kinase had no significant effect.
Inhibition of protein kinase C, nonselective cation channels, and phosphodiesterase enhanced gastrin release and reduced calcium influx, suggesting basal phosphodiesterase activity.

Conclusions

The calcium-sensing receptor on G cells activates phospholipase C and nonselective cation channels, facilitating extracellular calcium influx.
Protein kinase C isozymes in G cells play a crucial role in regulating both gastrin secretion and phosphodiesterase activity.

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