# The Expression of F2RL1, P2RX2, P2RX3 and P2RY2 in the Esophagus of Patients with Gastroesophageal Reflux Disease and Their Relationship to Reflux Symptoms—A Pilot Study

## TL;DR

This pilot study explores how certain receptors in the esophagus relate to symptoms in patients with gastroesophageal reflux disease.

## Contribution

The study identifies specific receptor expression patterns in GERD subtypes that may explain symptom differences.

## Key findings

- PAR2 receptor expression was higher in ERD compared to NERD and controls.
- P2X2 and P2Y2 expression was higher in NERD than in ERD and controls.
- Receptor expression correlated with dilated intracellular spaces and symptom intensity in GERD patients.

## Abstract

Background: The current treatment of gastroesophageal reflux disease (GERD) is focused on decreasing gastric acid secretion. However, there is still a group of patients that do not respond to conventional therapy. Proteinase-activated receptors and purinergic receptors have been implicated in inflammation, visceral hyperalgesia and esophageal hypersensitivity. The aim of this study was to evaluate the esophageal expression of PAR2 (F2RL1) and P2RX2, P2RX3 and P2RY2 in GERD patients. Methods: A total of 53 patients with GERD and 9 healthy controls were enrolled in this study. The expression of the studied receptors was quantified using real-time PCR on esophageal biopsies from the patients with GERD and healthy controls. The correlation between the dilated intracellular spaces (DIS) score and patients’ quality of life was investigated. Results: PAR2 receptor expression was higher in ERD compared to NERD and controls (326.10 ± 112.30 vs. 266.90 ± 84.76 vs. 77.60 ± 28.50; NS). P2X2 exhibited the highest expression in NERD compared to ERD and controls (302.20 ± 82.94 vs. 40.18 ± 17.78 vs. 26.81 ± 10.27), similarly to P2Y2, which expression was higher in NERD than in ERD and controls (7321.00 ± 1651.00 vs. 5306.0 ± 1738.00 vs. 3476.00 ± 508.0). Conclusions: We found that the expression of F2RL1, P2RX2 and P2RY2 is positively correlated to the DIS score in GERD patients. Higher PAR2, P2X2 and P2Y2 expression could mediate the sensitization of the esophagus and may be associated with the higher intensity of symptoms perceived by NERD patients.