Abstract
Hydrogen sulfide (H2S) is a significant physiologic inhibitory neurotransmitter. The main goal of this research was to examine the contribution of diverse potassium (K+) channels and nitric oxide (NO) in mediating the H2S effect on electrical field stimulation (EFS)-induced neurogenic contractile responses in the lower esophageal sphincter (LES). EFS-induced contractile responses of rabbit isolated LES strips were recorded using force transducers in organ baths that contain Krebs–Henseleit solutions (20 ml). Cumulative doses of NaHS, L-cysteine, PAG, and AOAA were evaluated in NO-dependent and NO-independent groups. The experiments were conducted again in the presence of K+ channel blockers. In both NO-dependent and NO-independent groups, NaHS, L-cysteine, PAG, and AOAA significantly reduced EFS-induced contractile responses. In the NO-dependent group, the effect of NaHS and L-cysteine decreased in the presence of 4-AP, and also the effect of NaHS decreased in the NO-dependent and independent group in the presence of TEA. In the NO-independent group, K+ channel blockers didn’t change L-cysteine-induced relaxations. K+ channel blockers had no impact on the effects of PAG and AOAA. In addition, NaHS significantly relaxed 80-mM KCl-induced contractions, whereas L-cysteine, PAG, and AOAA did not. In the present study, H2S decreased the amplitudes of EFS-induced contraction responses. These results suggest that Kv channels and NO significantly contribute to exogenous H2S and endogenous H2S precursor L-cysteine inhibitory effect on lower esophageal sphincter smooth muscle.
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Data availability
The datasets created and/or analyzed during the current study are accessible from the corresponding author upon reasonable request.
Abbreviations
- 4-AP:
-
4-Aminopyridine
- AOAA:
-
Aminooxyacetic acid
- ATP:
-
Adenosine triphosphate
- CBS:
-
Cystathionine beta-synthase
- CO:
-
Carbon monoxide
- CSE:
-
Cystathionine gamma-lyase
- DMSO:
-
Dimethyl sulfoxide
- EFS:
-
Electrical field stimulation
- GI:
-
Gastrointestinal
- H2S:
-
Hydrogen sulfide
- K+ :
-
Potassium channel
- KCa :
-
Calcium-activated K+ channel
- Kir :
-
Inwardly rectifying K+ channel
- KV :
-
Voltage-gated K+ channel
- LES:
-
Lower esophageal sphincter
- L-NAME:
-
L-NG-Nitro arginine methyl ester
- NaHS:
-
Sodium hydrosulfide
- NANC:
-
Non-adrenergic, non-cholinergic
- NO:
-
Nitric oxide
- PAG:
-
Propargylglycine
- TEA:
-
Tetraethylammonium
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This study was supported by Ankara Yıldırım Beyazıt University research fund (project no: 2113).
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AK: performed the research, analyzed the data, interpreted results of experiments, and wrote and edited the initial manuscript; DSK: performed experiments, and revised manuscript. CIA: interpreted results of experiments, edited and revised manuscript. HK: participated and involved in interpretation of data, and final check of the draft and revised the manuscript. GSOF: supervisor of the study, was involved in concept, design, support of study, drafting and final checking of the manuscript. SOI: interpretation of the results, wrote the manuscript; YS: designed research, interpretation of the results. All authors read and approved the final manuscript. The authors declare that all data were generated in-house and that no paper mill was used.
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This study was presented as an oral presentation at the 26th National and 1st International Pharmacology Congress, 2021, and as a poster presentation at 19th World Congress of Basic & Clinical Pharmacology, 2023.
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Koc, A., Koc, D.S., Askin, C.I. et al. Effects of hydrogen sulfide on relaxation responses in the lower esophageal sphincter in rabbits: the potential role of potassium channels. Naunyn-Schmiedeberg's Arch Pharmacol 397, 1537–1550 (2024). https://doi.org/10.1007/s00210-023-02695-z
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DOI: https://doi.org/10.1007/s00210-023-02695-z