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

Yıl 2023, Cilt: 4 Sayı: 2, 17 - 23, 13.09.2023

Öz

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.

Kaynakça

  • 1. Irwin GM. Urinary Incontinence. Prim Care. 2019;46:233-242.
  • 2. Andersson KE, Wein AJ. Pharmacology of the lower urinary tract: basis for current and future treatments of urinary incontinence. Pharmacol Rev. 2004;56:581-631.
  • 3. Shin JM, Sachs G. Pharmacology of proton pump inhibitors. Curr Gastroenterol Rep. 2008;10:528-534.
  • 4. Boparai V, Rajagopalan J, Triadafilopoulos G. Guide to the use of proton pump inhibitors in adult patients. Drugs. 2008;68:925-947.
  • 5. Terranova C, Petrella C, Improta G, Severini C, Signore F, Damiani P et al. Relaxant effect of proton pump inhibitors on in vitro myometrium from pregnant women. Eur J Pharm Sci. 2014;52:125-131.
  • 6. Bagcivan I, Gokce G, Ayan S, Yildirim S, Sarac B, Kilicarslan H et al. Hydrogen-potassium ATPase inhibitors induce relaxation on rabbit prostatic strips in vitro. Int J Urol. 2002;9:641-644.
  • 7. Kelicen P, Pekiner C, Sarioglu Y, Uma S. Omeprazole-induced relaxation in rat aorta is partly dependent on endothelium. Pharmacol Res. 2002;46:321-323.
  • 8. Duman M, Ozer M, Reyhan E, Demirci Y, Atici AE, Dalgic T et al. In vitro effect of pantoprazole on lower esophageal sphincter tone in rats. World J Gastroenterol. 2011;17:5105-5109.
  • 9. Okabe S, Amagase K, Fujita H, Iwata K, Satake N, Shibata S. Vasoinhibitory effect of leminoprazole, a H+,K(+)-ATPase inhibitor, on rat aortic rings. Gen Pharmacol. 1996;27:117-121.
  • 10. Sarioglu Y, Yildirim S, Utkan T, Yildirim MK, Uma S. Evidence of relaxant effect of omeprazole in rabbit corpus cavernosum in vitro. Life Sci. 2000;66:1411-1421.
  • 11. Kurt A, Altun A, Bagcivan I, Koyuncu A, Topcu O, Aydin C et al. Effects of proton pump inhibitors and h(2) receptor antagonists on the ileum motility. Gastroenterol Res Pract. 2011;218-342.
  • 12. Parsons C, Johnston S, Mathie E, Baron N, Machen I, Amador S ve diğ. Potentially inappropriate prescribing in older people with dementia in care homes: a retrospective analysis. Drugs Aging. 2012;29:143-155.
  • 13. Zhang X, Zhou S, Pan K, Li X, Zhao X, Zhou Y et al. Potentially inappropriate medications in hospitalized older patients: a cross-sectional study using the Beers 2015 criteria versus the 2012 criteria. Clin Interv Aging. 2017;12:16971703.
  • 14. Boucherie Q, Rouby F, Frankel D, Roll P, Micallef J. Proton pump inhibitors prescriptions in France: Main trends from 2006 to 2016 on French health insurance database. Therapie. 2018;73:385-388.
  • 15. Freedberg DE, Kim LS, Yang YX. The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice From the American Gastroenterological Association. Gastroenterology. 2017;152:706715.
  • 16. Kinoshita Y, Ishimura N, Ishihara S. Advantages and Disadvantages of Longterm Proton Pump Inhibitor Use. J Neurogastroenterol Motil. 2018;24:182196.
  • 17. Clark DW, Strandell J. Myopathy including polymyositis: a likely class adverse effect of proton pump inhibitors? Eur J Clin Pharmacol. 2006;62:473-479.
  • 18. Vinke P, Wesselink E, van Orten-Luiten W, van Norren K. The Use of Proton Pump Inhibitors May Increase Symptoms of Muscle Function Loss in Patients with Chronic Illnesses. Int J Mol Sci. 2020; 21(1).
  • 19. Aydin C, Sarac B, Koyuncu A, Yildirim S, Sen M, Sarioglu Y. Relaxant effect of omeprazole and lansoprazole in guinea pig gallbladder muscle strips in vitro. J Gastroenterol. 2003;38:765-771.
  • 20. Naseri E, Yenisehirli A. Proton pump inhibitors omeprazole and lansoprazole induce relaxation of isolated human arteries. Eur J Pharmacol. 2006;531:226231.
  • 21. Wu C, Bayliss M, Newgreen D, Mundy AR, Fry CH. A comparison of the mode of action of ATP and carbachol on isolated human detrusor smooth muscle. J Urol. 1999;162:1840-1847.
  • 22. Fry CH, Skennerton D, Wood D, Wu C. The cellular basis of contraction in human detrusor smooth muscle from patients with stable and unstable bladders. Urology. 2002;59:3-12.
  • 23. Schneider T, Fetscher C, Krege S, Michel MC. Signal transduction underlying carbachol-induced contraction of human urinary bladder. J Pharmacol Exp Ther. 2004;309:1148-1153.
  • 24. Peters SL, Schmidt M, Michel MC. Rho kinase: a target for treating urinary bladder dysfunction? Trends Pharmacol Sci. 2006;27:492-497.
  • 25. Li B, Wang R, Wang Y, Stief CG, Hennenberg M. Regulation of smooth muscle contraction by monomeric non-RhoA GTPases. Br J Pharmacol. 2020;177:3865-3877.
  • 26. Wibberley A, Chen Z, Hu E, Hieble JP, Westfall TD. Expression and functional role of Rho-kinase in rat urinary bladder smooth muscle. Br J Pharmacol. 2003;138:757-766.
  • 27. Wang R, Yu Q, Wang X, Li B, Ciotkowska A, Rutz B et al. Rac1 silencing, NSC23766 and EHT1864 reduce growth and actin organization of bladder smooth muscle cells. Life Sci. 2020;261:118468.
  • 28. Wang RX, Wang XL, Ciotkowska A, Rutz B, Tamalunas A, Gratzke C et al. Rac1 Inhibition by Eht1864, Nsc23766 or by Knockdown of Rac1 Expression Reduces Proliferation and Actin Organization in Human Bladder Smooth Muscle Cells. Journal of Urology. 2019;201:130-131.
  • 29. Semenov I, Herlihy JT, Brenner R. In vitro measurements of tracheal constriction using mice. J Vis Exp. 2012;64.
  • 30. Benarroch EE. Neural control of the bladder: recent advances and neurologic implications. Neurology. 2010;75:1839-1846.
  • 31. Kwon TH, Jung H, Cho EJ, Jeong JH, Sohn UD. The Signaling Mechanism of Contraction Induced by ATP and UTP in Feline Esophageal Smooth Muscle Cells. Mol Cells. 2015;38:616-623.
  • 32. Li B, Yu Q, Wang R, Gratzke C, Wang X, Spek A et al. Inhibition of Female and Male Human Detrusor Smooth Muscle Contraction by the Rac Inhibitors EHT1864 and NSC23766. Front Pharmacol. 2020;11:409.

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

Yıl 2023, Cilt: 4 Sayı: 2, 17 - 23, 13.09.2023

Öz

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.

Kaynakça

  • 1. Irwin GM. Urinary Incontinence. Prim Care. 2019;46:233-242.
  • 2. Andersson KE, Wein AJ. Pharmacology of the lower urinary tract: basis for current and future treatments of urinary incontinence. Pharmacol Rev. 2004;56:581-631.
  • 3. Shin JM, Sachs G. Pharmacology of proton pump inhibitors. Curr Gastroenterol Rep. 2008;10:528-534.
  • 4. Boparai V, Rajagopalan J, Triadafilopoulos G. Guide to the use of proton pump inhibitors in adult patients. Drugs. 2008;68:925-947.
  • 5. Terranova C, Petrella C, Improta G, Severini C, Signore F, Damiani P et al. Relaxant effect of proton pump inhibitors on in vitro myometrium from pregnant women. Eur J Pharm Sci. 2014;52:125-131.
  • 6. Bagcivan I, Gokce G, Ayan S, Yildirim S, Sarac B, Kilicarslan H et al. Hydrogen-potassium ATPase inhibitors induce relaxation on rabbit prostatic strips in vitro. Int J Urol. 2002;9:641-644.
  • 7. Kelicen P, Pekiner C, Sarioglu Y, Uma S. Omeprazole-induced relaxation in rat aorta is partly dependent on endothelium. Pharmacol Res. 2002;46:321-323.
  • 8. Duman M, Ozer M, Reyhan E, Demirci Y, Atici AE, Dalgic T et al. In vitro effect of pantoprazole on lower esophageal sphincter tone in rats. World J Gastroenterol. 2011;17:5105-5109.
  • 9. Okabe S, Amagase K, Fujita H, Iwata K, Satake N, Shibata S. Vasoinhibitory effect of leminoprazole, a H+,K(+)-ATPase inhibitor, on rat aortic rings. Gen Pharmacol. 1996;27:117-121.
  • 10. Sarioglu Y, Yildirim S, Utkan T, Yildirim MK, Uma S. Evidence of relaxant effect of omeprazole in rabbit corpus cavernosum in vitro. Life Sci. 2000;66:1411-1421.
  • 11. Kurt A, Altun A, Bagcivan I, Koyuncu A, Topcu O, Aydin C et al. Effects of proton pump inhibitors and h(2) receptor antagonists on the ileum motility. Gastroenterol Res Pract. 2011;218-342.
  • 12. Parsons C, Johnston S, Mathie E, Baron N, Machen I, Amador S ve diğ. Potentially inappropriate prescribing in older people with dementia in care homes: a retrospective analysis. Drugs Aging. 2012;29:143-155.
  • 13. Zhang X, Zhou S, Pan K, Li X, Zhao X, Zhou Y et al. Potentially inappropriate medications in hospitalized older patients: a cross-sectional study using the Beers 2015 criteria versus the 2012 criteria. Clin Interv Aging. 2017;12:16971703.
  • 14. Boucherie Q, Rouby F, Frankel D, Roll P, Micallef J. Proton pump inhibitors prescriptions in France: Main trends from 2006 to 2016 on French health insurance database. Therapie. 2018;73:385-388.
  • 15. Freedberg DE, Kim LS, Yang YX. The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice From the American Gastroenterological Association. Gastroenterology. 2017;152:706715.
  • 16. Kinoshita Y, Ishimura N, Ishihara S. Advantages and Disadvantages of Longterm Proton Pump Inhibitor Use. J Neurogastroenterol Motil. 2018;24:182196.
  • 17. Clark DW, Strandell J. Myopathy including polymyositis: a likely class adverse effect of proton pump inhibitors? Eur J Clin Pharmacol. 2006;62:473-479.
  • 18. Vinke P, Wesselink E, van Orten-Luiten W, van Norren K. The Use of Proton Pump Inhibitors May Increase Symptoms of Muscle Function Loss in Patients with Chronic Illnesses. Int J Mol Sci. 2020; 21(1).
  • 19. Aydin C, Sarac B, Koyuncu A, Yildirim S, Sen M, Sarioglu Y. Relaxant effect of omeprazole and lansoprazole in guinea pig gallbladder muscle strips in vitro. J Gastroenterol. 2003;38:765-771.
  • 20. Naseri E, Yenisehirli A. Proton pump inhibitors omeprazole and lansoprazole induce relaxation of isolated human arteries. Eur J Pharmacol. 2006;531:226231.
  • 21. Wu C, Bayliss M, Newgreen D, Mundy AR, Fry CH. A comparison of the mode of action of ATP and carbachol on isolated human detrusor smooth muscle. J Urol. 1999;162:1840-1847.
  • 22. Fry CH, Skennerton D, Wood D, Wu C. The cellular basis of contraction in human detrusor smooth muscle from patients with stable and unstable bladders. Urology. 2002;59:3-12.
  • 23. Schneider T, Fetscher C, Krege S, Michel MC. Signal transduction underlying carbachol-induced contraction of human urinary bladder. J Pharmacol Exp Ther. 2004;309:1148-1153.
  • 24. Peters SL, Schmidt M, Michel MC. Rho kinase: a target for treating urinary bladder dysfunction? Trends Pharmacol Sci. 2006;27:492-497.
  • 25. Li B, Wang R, Wang Y, Stief CG, Hennenberg M. Regulation of smooth muscle contraction by monomeric non-RhoA GTPases. Br J Pharmacol. 2020;177:3865-3877.
  • 26. Wibberley A, Chen Z, Hu E, Hieble JP, Westfall TD. Expression and functional role of Rho-kinase in rat urinary bladder smooth muscle. Br J Pharmacol. 2003;138:757-766.
  • 27. Wang R, Yu Q, Wang X, Li B, Ciotkowska A, Rutz B et al. Rac1 silencing, NSC23766 and EHT1864 reduce growth and actin organization of bladder smooth muscle cells. Life Sci. 2020;261:118468.
  • 28. Wang RX, Wang XL, Ciotkowska A, Rutz B, Tamalunas A, Gratzke C et al. Rac1 Inhibition by Eht1864, Nsc23766 or by Knockdown of Rac1 Expression Reduces Proliferation and Actin Organization in Human Bladder Smooth Muscle Cells. Journal of Urology. 2019;201:130-131.
  • 29. Semenov I, Herlihy JT, Brenner R. In vitro measurements of tracheal constriction using mice. J Vis Exp. 2012;64.
  • 30. Benarroch EE. Neural control of the bladder: recent advances and neurologic implications. Neurology. 2010;75:1839-1846.
  • 31. Kwon TH, Jung H, Cho EJ, Jeong JH, Sohn UD. The Signaling Mechanism of Contraction Induced by ATP and UTP in Feline Esophageal Smooth Muscle Cells. Mol Cells. 2015;38:616-623.
  • 32. Li B, Yu Q, Wang R, Gratzke C, Wang X, Spek A et al. Inhibition of Female and Male Human Detrusor Smooth Muscle Contraction by the Rac Inhibitors EHT1864 and NSC23766. Front Pharmacol. 2020;11:409.
Toplam 32 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Tıbbi Farmakoloji
Bölüm Araştırma makalesi
Yazarlar

Hakan Balcı Bu kişi benim

Bahar Akyüz Bu kişi benim

Süleyman Sırrı Bilge Bu kişi benim

Erken Görünüm Tarihi 15 Temmuz 2023
Yayımlanma Tarihi 13 Eylül 2023
Gönderilme Tarihi 5 Ocak 2023
Yayımlandığı Sayı Yıl 2023 Cilt: 4 Sayı: 2

Kaynak Göster

AMA Balcı H, Akyüz B, Bilge SS. The Effect of Omeprazole on Isolated Rat Bladder Detrusor Muscle and the Role of the Rac-1 Pathway in This Effect. YIU Saglik Bil Derg. Eylül 2023;4(2):17-23.