Endogenous cyclo-oxygenase activity regulates mouse gastric surface pH.

Area of Science:

• Gastroenterology
• Physiology
• Biochemistry

Background:

• Prostaglandin production by cyclo-oxygenase (COX) is crucial for gastric mucosal defense.
• The role of endogenous COX activity in regulating gastric surface pH remains to be fully elucidated.

Purpose of the Study:

• To investigate whether endogenous COX activity is essential for protective gastric surface pH control.
• To determine the specific COX enzyme isoforms involved in regulating gastric alkali secretion.

Main Methods:

• Perfusing intact mouse stomachs with solutions of varying pH and measuring gastric effluent pH and secretion.
• Utilizing in vivo confocal microscopy to image pH at the gastric mucosal surface.
• Administering COX inhibitors (indomethacin, SC-560, NS-398) and prostaglandin E2 (dm-PGE2) to assess their effects on pH and secretion.

Main Results:

• Gastric secretion switched from net acid to net alkali between pH 4 and 5.
• Non-specific COX inhibition (indomethacin) and COX-1 inhibition (SC-560) abolished net alkali secretion at pH 3, while COX-2 inhibition (NS-398) did not.
• Alkali secretion and protective alkaline surface pH were restored by dm-PGE2 treatment.
• Indomethacin acidified the gastric surface pH at pH 3, an effect reversed by dm-PGE2.

Conclusions:

• Endogenous cyclo-oxygenase (COX) activity, particularly COX-1, is critical for regulating the pre-epithelial alkaline layer in the stomach.
• Prostaglandins produced via COX activity play a vital role in maintaining gastric surface pH homeostasis.
• Targeting COX enzymes may offer therapeutic strategies for managing gastric acid-related disorders.