A protective role of protease-activated receptor 1 in rat gastric mucosa

Area of Science:

• Gastroenterology
• Pharmacology
• Cellular Biology

Background:

• Protease-activated receptor-2 (PAR-2) is known to protect gastric mucosa via sensory neurons.
• The role of protease-activated receptor-1 (PAR-1), a thrombin receptor, in gastric function is unexplored.
• This study investigates PAR-1's potential protective effects on the gastric lining.

Purpose of the Study:

• To determine if a PAR-1 agonist can prevent gastric mucosal damage in a rat model.
• To elucidate the mechanisms underlying PAR-1-mediated gastric protection.

Main Methods:

• Gastric mucosal injury was induced using ethanol/HCl or absolute ethanol in rats.
• Gastric mucosal blood flow and acid secretion were measured.
• Immunohistochemistry was used to detect PAR-1 and cyclooxygenase-1 (COX-1) expression in rat and human gastric tissues.

Main Results:

• The PAR-1 agonist, TFLLR-NH(2), significantly protected against ethanol-induced gastric injury.
• This protective effect was dependent on cyclooxygenase-1 (COX-1) activity, as it was blocked by indomethacin or a COX-1 inhibitor.
• PAR-1 activation increased gastric mucosal blood flow and suppressed acid secretion, independent of sensory neurons.
• PAR-1 and COX-1 were found in the muscularis mucosae and smooth muscle of rat and human stomachs.

Conclusions:

• Systemic PAR-1 activation offers protection against gastric mucosal injury.
• The mechanism involves COX-1-dependent prostanoid formation, impacting gastric blood flow and acid secretion.
• PAR-1 represents a novel target for gastric protection, with a mechanism distinct from PAR-2.