Evidence for the involvement of 5-HT2A receptors in mild mesenteric ischemia/reperfusion dysfunctions in mice

Area of Science:

• Gastroenterology
• Pharmacology
• Cardiovascular Research

Background:

• Mesenteric ischemia-reperfusion (I/R) injury is a serious clinical condition.
• The role of specific serotonin (5-HT) receptor subtypes in I/R injury remains incompletely understood.
• 5-HT2A receptors are implicated in various physiological and pathological processes.

Purpose of the Study:

• To investigate the involvement of the 5-HT2A receptor in mediating mesenteric I/R injury in a mouse model.
• To determine the therapeutic potential of targeting 5-HT2A receptors in I/R-induced gastrointestinal damage.

Main Methods:

• Established a mouse model of mesenteric I/R injury by occluding the superior mesenteric artery.
• Administered the 5-HT2A antagonist ketanserin or the 5-HT2A agonist DOI before ischemia and during reperfusion.
• Assessed gastrointestinal transit, leukocyte recruitment (myeloperoxidase activity), vascular permeability (Evans Blue extravasation), and platelet aggregation.

Main Results:

• Ketanserin administration significantly prevented I/R-induced gastrointestinal transit delay, reduced neutrophil infiltration in the jejunum, and decreased vascular leakage in multiple organs.
• Activation of 5-HT2A receptors by DOI mimicked I/R effects, causing prolonged transit and increased neutrophil accumulation.
• Ketanserin treatment also preserved ADP-induced platelet aggregation in I/R mice.

Conclusions:

• The 5-HT2A receptor subtype plays a critical role in the pathophysiology of mesenteric I/R injury.
• Selective antagonism of 5-HT2A receptors demonstrates a protective effect against I/R-induced damage.
• Targeting 5-HT2A receptors represents a potential therapeutic strategy for mesenteric I/R injury.