Background: Pain is a prominent symptom of gastroesophageal reflux disease (GERD)
and commonly related to acidic reflux. 5-ydroxytryptamin (5-HT), a neurotransmitter
and ligand for 5-HT receptors (5-HTR) is an activator of acid sensing ion channels
(ASICs).We reported earlier [1] that gene expressions of ASIC4 and 5-HTR-subtypes were simultaneously regulated
in the esophageal mucosa and hypothesized that both ASICs and 5-HTRs- play a role
for the fast pain relief in responders to STW 5, a herbal multicomponent mixture,
and the PPI Omeprazole (O).
Aims: Comparison of gene- and protein expressions of ASICs, 5-HTRs, 5-HT and serotonin
transporters (SERT) in rat model GERD [2] by Western Blot (WB); detection of ASIC4 and 5-HT in human esophageal biopsies [endoscopically
normal (n = 18), inflamed (n = 16)] by immunohistochemistry (IH).
Results: issues of animals suffering from GERD showed small, but significant increases
in the gene expression of ASIC-subtype 4 (3.8f), of HTR2A (3fold), HTR2B (6.6f), HTR7
(9.3f) (p < 0.001) and a downregulation of SERT (−2.4f, p < 0.001) compared to ‘normal’
tissue. In tissues of animals treated with either STW5 (2ml/kg) or with O (30mg/kg),
ASIC 4 (−4,8f, −4f; p < 0.0001), HTR2A (−5.4f, −3.9f) HTR2B (−7.9f, 3.7f) and HTR7
were downregulated (p < 0.0001) respectively. Reductions of HTR7 by O (−6.8f) was
less compared to STW5 (−15.4f) and did not match the upregulation during inflammation.
In human esophageal biopsies ASIC 4 was detected in normal and inflamed tissue, 5-HT
only in inflamed tissue.
Conclusion: IH and WB of ASIC4, HTR-subtypes and SERT supported gene expression data
and thereby a corporate role in the esophageal nociception.
