The Copper (I) Chelator Neocuproine Inhibits Mouse Bladder Function, but not the Copper (II) Chelator Cuprizone
Yıl: 2021 Cilt: 43 Sayı: 5 Sayfa Aralığı: 439 - 447 Metin Dili: İngilizce DOI: 10.20515/otd.894353 İndeks Tarihi: 07-09-2022
The Copper (I) Chelator Neocuproine Inhibits Mouse Bladder Function, but not the Copper (II) Chelator Cuprizone
Öz: The aim of this study was to investigate the effect of neocuproine (NC), a selective Cu(I) chelator, on the spontaneous contractions (SC) and basal tension (BT) in isolated mouse bladder tissues. The spontaneous contractions and basal tension in the isolated bladder strips were recorded to evaluate the amplitude and frequency parameters. NC (100 μM) caused a significant inhibition on spontaneous contractions (SC) in the isolated mouse bladder. We also evaluated the effects of cuprizone, a selective Cu(II)-chelator, and various selective or non-selective purinoceptor antagonists on the SC and also on the basal tension (BT). Of them, a non-selective purinergic antagonist suramin, a P2X receptor antagonist PPADS, a P2X3 antagonist NF 110, a P2 receptor activator ATP or a P2Y1 antagonist MRS 2179 significantly reversed NC-induced inhibition on the SC whereas cuprizone was found ineffective. The results showed that both P2X and P2Y receptors are playing role in the inhibitory effect of NC on the mouse bladder function. Ca2+ addition to the organ bath medium also dose-dependently reversed the NC-induced inhibition suggesting the role of myogenic mechanism. These findings suggest that intracellular calcium reduction, purinergic pathway and Cu(I) but not Cu(II) may have an important role in the inhibitory activity of NC on mouse bladder function
Anahtar Kelime: Bakır (I) Şelatörü Neocuproine Fare Mesane Fonksiyonunu İnhibe Eder, Ancak Bakır (II) Şelatörü Cuprizone İnhibe Etmez
Öz: Bu çalışmanın amacı, seçici bir Cu(I) şelatörü olan neocuproine’in (NC) izole fare mesane dokularındaki spontan kasılmalar (SK) ve bazal gerginlik (BT) üzerindeki etkisini araştırmaktır. İzole mesane striplerinde spontan kasılmalar ve bazal tonus, amplitude ve frekans parametreleri değerlendirilmiştir. Ayrıca selektif bir Cu(II)-şelatör olan cuprizone’un ve çeşitli selektif ve nonselektif purinoseptör antagonistlerinin spontan kasılmalar ve bazal tonus (BT) üzerindeki etkileri de değerlendirildi. NC (100 μM), izole edilmiş fare mesanesinde spontan kasılmalar üzerinde önemli bir inhibisyona neden olmuştur. Bunlardan nonselektif bir purinerjik antagonist olan suramin, bir P2X reseptör antagonisti PPADS, bir P2X3 antagonisti NF 110, bir P2 reseptör aktivatörü ATP veya bir P2Y1 antagonisti MRS 2179, spontan kasılmalar üzerinde NC'in neden olduğu inhibisyonu önemli ölçüde tersine çevirirken cuprizone etkisiz bulundu. Sonuçlar, NC'nin fare mesane işlevi üzerindeki inhibitör etkisinde hem P2X hem de P2Y reseptörlerinin rol oynadığını göstermektedir. Organ banyosu ortamına Ca2+ ilavesi de doza bağlı olarak NC ile indüklenen inhibisyonu tersine çevirerek miyojenik mekanizmanın rolü olabileceğini düşündürdü. Bu bulgular, hücre içi kalsiyum azalmasının, purinerjik yolun ve Cu(I) 'in, fare mesane fonksiyonu üzerindeki NC'nin inhibe edici aktivitesinde önemli bir role sahip olabildiğini, Cu(II)' nin etkisiz olduğunu göstermektedir
Anahtar Kelime: Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
- 1. Burnstock G. Purinergic signalling in the urinary tract in health and disease. Purinergic Signalling 2014;10:103–55.
- 2. Virgilio F Di, Sarti AC, Coutinho-Silva R. Purinergic signaling, DAMPs, and inflammation. American Journal of Physiology - Cell Physiology 2020;318:C832–5.
- 3. Ueda N, Kondo M, Takezawa K, et al. Bladder urothelium converts bacterial lipopolysaccharide information into neural signaling via an ATP- mediated pathway to enhance the micturition reflex for rapid defense. Scientific Reports 2020;10:1–15.
- 4. Burnstock G. Introduction: ATP and Its Metabolites as Potent Extracellular Agents. Current Topics in Membranes 2003;54:1–27.
- 5. Kennedy C. The P2Y/P2X divide: How it began. Biochem Pharmacol. 2021;187:114408
- 6. Alexander SPH, Mathie A, Peters JA, et al. The Concıse Guıde to Pharmacology 2019/20: Ion channels. British Journal of Pharmacology 2019;176:S142–228.
- 7. Illes P, Müller CE, Jacobson KA, et al. Update of P2X receptor properties and their pharmacology: Iuphar Review 30. British Journal of Pharmacology 2020;178:489–514.
- 8. Burnstock G. Therapeutic potential of purinergic signalling for diseases of the urinary tract. BJU International 2011;107:192–204.
- 9. Sui G, Fry CH, Montgomery B, Roberts M, Wu R, Wu C. Purinergic and muscarinic modulation of ATP release from the urothelium and its paracrine actions. American Journal of Physiology - Renal Physiology 2014;306:F286–98.
- 10. Chopra B, Gever J, Barrick SR, et al. Expression and function of rat urothelial P2Y receptors. American Journal of Physiology-Renal Physiology 2008;294:F821–9.
- 11. Shabir S, Cross W, Kirkwood LA, et al. Functional expression of purinergic P2 receptors and transient receptor potential channels by the human urothelium. American Journal of Physiology-Renal Physiology 2013;305:F396– 406.
- 12. Everaerts W, Vriens J, Owsianik G, et al. Functional characterization of transient receptor potential channels in mouse urothelial cells. American Journal of Physiology - Renal Physiology 2010;298:692–701.
- 13. Ding X, Xie H, Kang YJ. The significance of copper chelators in clinical and experimental application. Journal of Nutritional Biochemistry 2011;22:301–10.
- 14. Arnal N, De Alaniz MJT, Marra CA. Carnosine and neocuproine as neutralizing agents for copper overload-induced damages in cultured human cells. Chemico-Biological Interactions 2011;192:257–63.
- 15. De Man JG, Moreels TG, De Winter BY, Herman AG, Pelckmans PA. Neocuproine potentiates the activity of the nitrergic neurotransmitter but inhibits that of S-nitrosothiols. European Journal of Pharmacology 1999;381:151–9.
- 16. Göçmen C, Göktürk HS, Ertuǧ PU, Önder S, Dikmen A, Baysal F. Effect of neocuproine, a selective Cu(I) chelator, on nitrergic relaxations in the mouse corpus cavernosum. European Journal of Pharmacology 2000;406:293–300.
- 17. Göçmen C, Kumcu EK, Büyüknacar HS, Önder S, Singirik E. Neocuproine, a Copper (I) Chelator, Potentiates Purinergic Component of Vas Deferens Contractions Elicited by Electrical Field Stimulation. Pharmacology 2005;75:69–75.
- 18. Kumcu EK, Büyüknacar HSG, Göçmen C, Evrüke IC, Önder S. Differential effect of neocuproine, a copper(I) chelator, on contractile activity in isolated ovariectomized non-pregnant rat, pregnant rat and pregnant human uterus. European Journal of Pharmacology 2009;605:158–63.
- 19. Göçmen C, Giesselman B, De Groat WC. Effect of neocuproine, a copper(I) chelator, on rat bladder function. Journal of Pharmacology and Experimental Therapeutics 2005;312:1138–43.
- 20. Benkó R, Lázár Z, Pórszász R, Somogyi GT, Barthó L. Effect of experimental diabetes on cholinergic, purinergic and peptidergic motor responses of the isolated rat bladder to electrical field stimulation or capsaicin. European Journal of Pharmacology 2003;478:73–80.
- 21. Yu W, Hill WG, Robson SC, Zeidel ML. Role of P2X4 Receptor in Mouse Voiding Function. Scientific Reports 2018;8:1–11.
- 22. Thériault O, Poulin H, Thomas GR, Friesen AD, Al-Shaqha WA, Chahine M. Pyridoxal-5’- phosphate (MC-1), a vitamin B6 derivative, inhibits expressed P2X receptors. Canadian Journal of Physiology and Pharmacology 2014;92:189–96.
- 23. Ford AP, Smith SA, Dillon MP. Pharmadynamic (PD) & pharmacokinetic (PK) properties of AF- 219: first in class, selective, clinical P2X3 antagonist in development for chronic pain and related conditions. FASEB 2013.
- 24. Burnstock G. Purinergic signalling: Therapeutic developments. Frontiers in Pharmacology 2017;8:661.
- 25. Burnstock G. Short- and long-term (trophic) purinergic signalling. Philos Trans R Soc Lond B Biol Sci. 2016;371:20150422.
- 26. Kitajima S, Ozaki H, Karaki H. The effects of ATP and α,β-methylene-ATP on cytosolic Ca2+ level and force in rat isolated aorta. British Journal of Pharmacology 1993;110:263–8.
| APA | ESER N, Büyüknacar H, Kumcu E, göçmen c (2021). The Copper (I) Chelator Neocuproine Inhibits Mouse Bladder Function, but not the Copper (II) Chelator Cuprizone. , 439 - 447. 10.20515/otd.894353 |
| Chicago | ESER Nadire,Büyüknacar Hacer Sinem,Kumcu Eda Karabal,göçmen cemil The Copper (I) Chelator Neocuproine Inhibits Mouse Bladder Function, but not the Copper (II) Chelator Cuprizone. (2021): 439 - 447. 10.20515/otd.894353 |
| MLA | ESER Nadire,Büyüknacar Hacer Sinem,Kumcu Eda Karabal,göçmen cemil The Copper (I) Chelator Neocuproine Inhibits Mouse Bladder Function, but not the Copper (II) Chelator Cuprizone. , 2021, ss.439 - 447. 10.20515/otd.894353 |
| AMA | ESER N,Büyüknacar H,Kumcu E,göçmen c The Copper (I) Chelator Neocuproine Inhibits Mouse Bladder Function, but not the Copper (II) Chelator Cuprizone. . 2021; 439 - 447. 10.20515/otd.894353 |
| Vancouver | ESER N,Büyüknacar H,Kumcu E,göçmen c The Copper (I) Chelator Neocuproine Inhibits Mouse Bladder Function, but not the Copper (II) Chelator Cuprizone. . 2021; 439 - 447. 10.20515/otd.894353 |
| IEEE | ESER N,Büyüknacar H,Kumcu E,göçmen c "The Copper (I) Chelator Neocuproine Inhibits Mouse Bladder Function, but not the Copper (II) Chelator Cuprizone." , ss.439 - 447, 2021. 10.20515/otd.894353 |
| ISNAD | ESER, Nadire vd. "The Copper (I) Chelator Neocuproine Inhibits Mouse Bladder Function, but not the Copper (II) Chelator Cuprizone". (2021), 439-447. https://doi.org/10.20515/otd.894353 |
| APA | ESER N, Büyüknacar H, Kumcu E, göçmen c (2021). The Copper (I) Chelator Neocuproine Inhibits Mouse Bladder Function, but not the Copper (II) Chelator Cuprizone. Osmangazi Tıp Dergisi, 43(5), 439 - 447. 10.20515/otd.894353 |
| Chicago | ESER Nadire,Büyüknacar Hacer Sinem,Kumcu Eda Karabal,göçmen cemil The Copper (I) Chelator Neocuproine Inhibits Mouse Bladder Function, but not the Copper (II) Chelator Cuprizone. Osmangazi Tıp Dergisi 43, no.5 (2021): 439 - 447. 10.20515/otd.894353 |
| MLA | ESER Nadire,Büyüknacar Hacer Sinem,Kumcu Eda Karabal,göçmen cemil The Copper (I) Chelator Neocuproine Inhibits Mouse Bladder Function, but not the Copper (II) Chelator Cuprizone. Osmangazi Tıp Dergisi, vol.43, no.5, 2021, ss.439 - 447. 10.20515/otd.894353 |
| AMA | ESER N,Büyüknacar H,Kumcu E,göçmen c The Copper (I) Chelator Neocuproine Inhibits Mouse Bladder Function, but not the Copper (II) Chelator Cuprizone. Osmangazi Tıp Dergisi. 2021; 43(5): 439 - 447. 10.20515/otd.894353 |
| Vancouver | ESER N,Büyüknacar H,Kumcu E,göçmen c The Copper (I) Chelator Neocuproine Inhibits Mouse Bladder Function, but not the Copper (II) Chelator Cuprizone. Osmangazi Tıp Dergisi. 2021; 43(5): 439 - 447. 10.20515/otd.894353 |
| IEEE | ESER N,Büyüknacar H,Kumcu E,göçmen c "The Copper (I) Chelator Neocuproine Inhibits Mouse Bladder Function, but not the Copper (II) Chelator Cuprizone." Osmangazi Tıp Dergisi, 43, ss.439 - 447, 2021. 10.20515/otd.894353 |
| ISNAD | ESER, Nadire vd. "The Copper (I) Chelator Neocuproine Inhibits Mouse Bladder Function, but not the Copper (II) Chelator Cuprizone". Osmangazi Tıp Dergisi 43/5 (2021), 439-447. https://doi.org/10.20515/otd.894353 |
