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

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 nonselective 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.