Planta Med 2019; 85(18): 1416
DOI: 10.1055/s-0039-3399706
Abstracts of Short Lectures
Short Lectures Tuesday, September 03, 2019
Short Lectures F: Biological and Pharmacological Activities of Natural Products (Mixed)
© Georg Thieme Verlag KG Stuttgart · New York

Regulations of ASIC 4, 5-HTR and SERT in the esophageal mucosa under STW5 treatment support a corporate role in pain sensing

G Ulrich-Merzenich
1   Medical Clinic III, University Hospital Bonn, University of Bonn, Venusberg Campus 1, 53127 Bonn, Germany
,
L Welslau
1   Medical Clinic III, University Hospital Bonn, University of Bonn, Venusberg Campus 1, 53127 Bonn, Germany
,
O Kelber
2   Scientific Department, Innovation and Development, Steigerwald Arzeneimittelwerk GmbH, Bayer Consumer Health, Havelstrasse 5, 64238 Darmstadt, Germany
,
A Sherbakova
1   Medical Clinic III, University Hospital Bonn, University of Bonn, Venusberg Campus 1, 53127 Bonn, Germany
3   Department of Forestry, Volga State University of Technology, Lenin sqn 3, 424020 Yoshkar-Ola, Russia
,
C Esch
4   Institute of Pathology, UKB, Bonn University, Venusberg Campus 1, 53127 Bonn, Germany
,
T Thiesler
4   Institute of Pathology, UKB, Bonn University, Venusberg Campus 1, 53127 Bonn, Germany
,
HP Fischer
4   Institute of Pathology, UKB, Bonn University, Venusberg Campus 1, 53127 Bonn, Germany
,
G Kristiansen
4   Institute of Pathology, UKB, Bonn University, Venusberg Campus 1, 53127 Bonn, Germany
,
A Meguid Kassem
5   Tropical Medicine Dept. and Gastrointestinal Endoscopy Unit, Faculty of Medicine, Kairo, Egypt
,
H Aziz-Kalbhenn
2   Scientific Department, Innovation and Development, Steigerwald Arzeneimittelwerk GmbH, Bayer Consumer Health, Havelstrasse 5, 64238 Darmstadt, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
20 December 2019 (online)

Also available at
 

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.
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