Koc Aysegul, Koc Derya Sebile, Askin Celil Ilker, Kara Halil, Ozturk Fincan Gokce Sevim, Ozger Ilhan Sevil, Sarioglu Yusuf
Department of Medical Pharmacology, Faculty of Medicine, Ankara Yıldırım Beyazıt University, Ankara, Turkey.
Department of Medical Pharmacology, Faculty of Medicine, Gazi University, Ankara, Turkey.
Naunyn Schmiedebergs Arch Pharmacol. 2024 Mar;397(3):1537-1550. doi: 10.1007/s00210-023-02695-z. Epub 2023 Sep 5.
Hydrogen sulfide (HS) 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 HS 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, HS decreased the amplitudes of EFS-induced contraction responses. These results suggest that Kv channels and NO significantly contribute to exogenous HS and endogenous HS precursor L-cysteine inhibitory effect on lower esophageal sphincter smooth muscle.
硫化氢（HS）是一种重要的生理性抑制性神经递质。本研究的主要目的是探讨多种钾（K）通道和一氧化氮（NO）在介导HS对下食管括约肌（LES）电场刺激（EFS）诱导的神经源性收缩反应中的作用。使用器官浴槽中的力传感器记录兔离体LES条带的EFS诱导的收缩反应，浴槽中含有Krebs-Henseleit溶液（20毫升）。在NO依赖性和NO非依赖性组中评估了NaHS、L-半胱氨酸、PAG和AOAA的累积剂量。在存在K通道阻滞剂的情况下再次进行实验。在NO依赖性和NO非依赖性组中，NaHS、L-半胱氨酸、PAG和AOAA均显著降低了EFS诱导的收缩反应。在NO依赖性组中，在存在4-AP的情况下，NaHS和L-半胱氨酸的作用减弱，并且在存在TEA的情况下，NO依赖性和非依赖性组中NaHS的作用均减弱。在NO非依赖性组中，K通道阻滞剂未改变L-半胱氨酸诱导的舒张。K通道阻滞剂对PAG和AOAA的作用没有影响。此外，NaHS显著舒张了80 mM KCl诱导的收缩，而L-半胱氨酸、PAG和AOAA则没有。在本研究中，HS降低了EFS诱导的收缩反应幅度。这些结果表明，Kv通道和NO对外源性HS和内源性HS前体L-半胱氨酸对下食管括约肌平滑肌的抑制作用有显著贡献。
