Effects of proglumide on pancreatic acinar cell function

Area of Science:

• Pharmacology
• Gastroenterology
• Neuroscience

Background:

• Cholecystokinin (CCK) plays a vital role in regulating pancreatic exocrine secretion and glucose homeostasis.
• Gastrin receptor antagonists are investigated for potential therapeutic applications.

Purpose of the Study:

• To investigate the antagonistic effects of proglumide on cholecystokinin (CCK) receptors.
• To determine the specificity and mechanism of proglumide's interaction with CCK receptors.

Main Methods:

• Isolated mouse pancreatic acini were used to assess amylase release and glucose uptake.
• Radioligand binding assays were performed to evaluate the inhibition of 125I-CCK binding to receptors.
• Effects on carbachol and insulin signaling pathways were examined.

Main Results:

• Proglumide competitively inhibited CCK-stimulated amylase release (KI = 0.7 mM) and [3H]-2-deoxy-D-glucose uptake.
• Proglumide competitively inhibited 125I-CCK binding to receptors in pancreas and brain (KI = 1.0 mM).
• Proglumide did not affect carbachol- or insulin-stimulated processes but showed non-specific effects at high concentrations.

Conclusions:

• Proglumide is a specific, competitive, but weak antagonist of CCK receptors.
• The findings support proglumide's role in modulating CCK signaling pathways.
• Non-specific effects of proglumide at higher concentrations warrant consideration.