The Copper (I) Chelator Neocuproine Inhibits Mouse Bladder Function, but not the Copper (II) Chelator Cuprizone

Year 2021, Volume: 43 Issue: 5, 439 - 447, 13.09.2021

Nadire Eser H.sinem Büyüknacar Eda Kumcu Cemil Göçmen

https://doi.org/10.20515/otd.894353

Abstract

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

Keywords

Bladder activity, neocuproine, copper(I) chelator, Cu(II)-chelator, mause, purinoceptors

Thanks

We would like to thank The Scientific and Technological Research Council of Turkey (TUBITAK) to support this study as a scholar of 1002 - Short Term R&D Funding Program (112S016).

Bakır (I) Şelatörü Neocuproine Fare Mesane Fonksiyonunu İnhibe Eder, Ancak Bakır (II) Şelatörü Cuprizone İnhibe Etmez

Abstract

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

Keywords

mesane aktivitesi, Neocuproine, Bakır (I) şelatörü, Fare, Purinoseptörler

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