Fare mide fundus dokusunda L-sistein/H2S yolağının KCl kasılma yanıtları üzerindeki etkisine nitrik oksid ve siklooksijenaz yolağının olası katkısı

Amaç:Çalışmamızda, fare mide fundus dokusunda L-sistein/ hidrojen sülfür (H2S) yolağının potasyum klorür (KCl) kasılma yanıtları üzerindeki etkisi ve bu etkide nitrik oksid (NO) ve siklooksijenaz (COX) yolaklarının olası katkılarının araştırılması amaçlanmıştır.Gereç ve Yöntem:İzole fare fundus şeritlerinde, kümülatif KCl (10-80 mM) ile kasılma yanıtları oluşturulup, L-sistein (10 mM)’in bu kasılma yanıtları üzerindeki etkisi incelendi. Ayrıca, H2S’in endojen olarak sentezine aracılık eden sistatyon beta-sentaz (CBS) enzim inhibitörü aminooksiasetik asid (AOAA; 1 mM) ve sistatyon gamma-liyaz (CSE) enzim inhibitörü proparjil glisin (PAG, 10 mM) varlığında, L-sistein ’in KCl kasılma yanıtları üzerindeki etkisi araştırıldı. L-sistein’in KCl kasılmaları üzerindeki etkisine NO ve COX yolaklarının olası katkısı, nitrik oksid sentaz (NOS) enzim inhibitörü L-Nitroarjinin (L-NA; 0.1 mM) ve non-selektif COX enzim inhibitörü indometazin (0.001 mM) varlığında incelendi. Bulgular: L-sistein, KCl kasılma yanıtlarında inhibe edici bir etki oluşturdu. AOAA, L-sistein ’in KCl kasılmaları üzerindeki inhibe edici etkisinin geri çevrilmesine neden oldu. PAG varlığında ise, L-sistein ’in düşük konsantrasyonlardaki KCl kasılma yanıtları üzerindeki inhibe edici etkisinin azaldığı gözlendi. L-NA içeren ortamda, L-sistein sadece maksimum KCl kasılma yanıtında bir inhibisyona neden oldu. Bu inhibe edici etki, AOAA ve PAG ile geri çevrildi. İndometazin ise, L-sistein ’in KCl kasılmaları üzerindeki düşük konsantrasyondaki inhibe edici etkisinin azalmasına neden oldu. Ayrıca, ortamda L-NA ile indometazin kombinasyonunu varlığında, L-sistein ’in kasılma yanıtları üzerinde neden olduğu inhibisyon PAG ve AOAA ile geri çevrildi. Sonuç:Bu bulgular, fare fundus dokusunda L-sistein/ H2S yolağının KCl kasılma yanıtları üzerinde inhibitör etkisinin olduğunu ve bu etkinin NO ve COX yolakları ile ilişkili olabileceğini düşündürmektedir.

Anahtar Kelimeler:

Fare, fundus, hidrojen sülfür, KCl, L-sistein, nitrik oksid

The possible contribution of NO and Cyclooxygenase pathways to the effect of L-cysteine/H2S pathway on the contractile response of KCl in mouse gastric fundus

Purpose:In the present study, was aimed at investigating the effect of L-cysteine/ hydrogen sulfide (H2S) pathway on contractile response to potassium chloride in mouse gastric fundus and possible contributions of nitric oxide (NO) and cyclooxygenase (COX) pathways in this effectMaterial and Methods:The contractile responses to cumulative KCl was produced in isolated mouse fundus strips and the effect of L-cysteine (10 mM) on this responses was examined. In addition, the effect of L-cysteine on the contractile responses to KCI were investigated in the presence cystathionine beta-synthase (CBS) enzyme inhibitor aminoxyacetic acid (AOAA; 1 mM) and cystathionine gamma-lyase (CSE) enzyme inhibitor propargyl glycine (PAG, 10 mM), which mediated the endogenously synthesize of H2S. The possible contribution of NO and COX pathways to the effect of L-cysteine on KCl contractions was examined in the presence of L-Nitroarginine (L-NA; 0.1 mM), a nitric oxide synthase inhibitor and indomethacin (0.001 M), a non-selective COX inhibitor. Results:L-cysteine significantly attenuated the contractile responses to KCl. The inhibitory effect of L-cysteine was significantly reversed by AOAA. However, PAG reduced the inhibitory effect of L-cysteine on the contractile responses to lower concentrations KCl. In the presence of L-NA, L-cysteine decreased the maximum contractile response to KCl and this inhibitory effect was reversed by AOAA and PAG. The inhibitory effect of L-cysteine on the contractile response to lower concentration of KCl was reversed in the presence indomethacin. Indeed, in the presence of L-NA and indomethacin combination, the inhibitory effect of L-cysteine on the contractile responses to KCl were reversed by PAG and AOAA pre-incubationConclusion:The findings of current study suggest that L-cystein/H2S pathway has an inhibitory effect on the contractile response to KCl and this effect may be related NO and COX pathways.

Keywords:

Cyclooxygenase fundus, hydrogen sulfide, KCl, mouse, L-cysteine, nitric oxide,

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