Hakan BALCI, Bahar AKYÜZ, Süleyman Sırrı BİLGE

İzole Sıçan Mesane Detrusor Kasında Omeprazolün Etkisi ve Bu Etkide Rac-1 Yolağının Rolü

Giriş: Omeprazol ve diğer proton pompası inhibitörlerini kullanan bazı hastalarda bildirilen üriner retansiyon problemi bu ilacın mesane düz kasını da gevşeterek bu etkiyi oluşturduğunu düşündürmektedir. Omeprazol ve diğer proton pompası inhibitörleri ile yapılan çalışmalarda bu ilaçların çeşitli doku ve organ düz kaslarında gevşemeye neden olduğunun gösterilmesi de hipotezimizi desteklemektedir. Fakat omeprazolün mesane düz kası üzerindeki olası etkisi ve etki mekanizmasıyla ilgili bir çalışmaya literatürde rastlanmamaktadır. Bu çalışmanın amacı omeprazolün izole sıçan mesane detrüsör kasındaki olası etki ve etki mekanizmasının araştırılmasıdır. Gereç ve Yöntem: 10-4, 5x10-4, 10-3 M omeprazol varlığında asetilkolin (10-6-10-3 M) ve elektriksel alan stimülasyonu (2-64 Hz) ile indüklenen kasılma yanıtları ölçüldü. Omeprazolün etki mekanizmasını araştırmak için rac-1 yolak inhibitörü NSC23799 (10-4 M) kullanıldı. İstatistiksel analiz için tek yönlü varyans analizi (ANOVA) ve TukeyKramer post-hoc test kullanıldı. Bulgular: Omeprazol (10-4, 5x10-4, 10-3 M) doza bağlı olarak asetilkolin ve elektriksel alan stimülasyonu ile indüklenen maksimum kasılma yanıtlarını anlamlı olarak inhibe etti. Omeprazolün (5x104 M) NSC23766 ile kombine uygulandığında tek başına NSC23766 uygulanan gruba göre ACh ve EFS ile indüklenen yanıtlarda anlamlı bir artış meydana getirdi. Sonuç: Bu sonuçlar omeprazolün izole sıçan detrusor kasındaki kasılmaları inhibe etmesinin rac-1 yolağının blokajı aracılığıyla olduğunu göstermektedir.

Anahtar Kelimeler:

Detrusor Kası, Omeprazol, Rac-1 Yolağı, Sıçan

The Effect of Omeprazole on Isolated Rat Bladder Detrusor Muscle and the Role of the Rac-1 Pathway in This Effect

Introduction: The urinary retention problem reported in some patients using omeprazole and other proton pump inhibitors suggests that this drug has this effect by relaxing the bladder smooth muscle. Studies with omeprazole and other proton pump inhibitors show that these drugs cause relaxation in various tissue and organ smooth muscles, which also supports our hypothesis. However, there is no study in the literature about the possible effect and mechanism of action of omeprazole on bladder smooth muscle. The aim of this study is to investigate the possible effect and mechanism of action of omeprazole in isolated rat bladder detrusor muscle. Materials and Methods: In the presence of omeprazole (10-4, 5x104, 10-3 M), contraction responses induced by acetylcholine (10-6-103 M) and electrical field stimulation (2-64 Hz) were measured. Rac1 pathway inhibitor NSC23799 (10-4 M) was used to investigate the mechanism of action of omeprazole. One-way analysis of variance (ANOVA) and Tukey-Kramer post-hoc test were used for statistical analysis. Results: Omeprazole (10-4, 5x10-4, 10-3 M) dose-dependently inhibited maximal contraction responses induced by acetylcholine and electrical field stimulation. When omeprazole (5x10-4 M) was applied in combination with NSC23766, it caused a significant increase in ACh and EFS-induced responses compared to the NSC23766 alone group. Conclusion: These results show that omeoprazole inhibits contractions in isolated rat detrusor muscle through blockade of rac-1 pathway.

Keywords:

Detrusor Muscle, Omeprazole, Rac-1 Pathway, Rat,

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