RSS-Feed abonnieren
DOI: 10.1055/s-0039-3399706
Regulations of ASIC 4, 5-HTR and SERT in the esophageal mucosa under STW5 treatment support a corporate role in pain sensing
Publikationsverlauf
Publikationsdatum:
20. Dezember 2019 (online)
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.
-
References
- 1 Ulrich-Merzenich G, Shcherbakova A, Kelber O. et al. Pain sensations in gastroesophageal reflux disease may be mediated by acid sensing ion channels- evidence for novel targets of STW5 derived from a rat model. Planta Med 2016; 81 (S01): S1-S381.
- 2 Abdel-Aziz H, Schneider M, Neuhuber W. et al. Mol Med 2015; 21: 1011-1024.