Received for publication August 19, 2004.
Revised October 21, 2004.
Accepted for publication October 21, 2004.

Effect of neocuproine, a copper (I) chelator, on rat bladder function

Abstract

The effects of a specific copper(I)-chelator, neocuproine (NC), and a selective copper(II)-chelator, cuprizone, on nonadrenergic-noncholinergic transmitter mechanisms in the rat urinary bladder were studied by measuring nerve-evoked contractions of bladder strips and voiding function under urethane anesthesia. After blocking cholinergic and adrenergic transmission with atropine and guanethidine, electrical field stimulation (EFS) induced bimodal contractions of bladder strips. An initial, transient contraction which was blocked by the purinergic antagonist, suramin, was significantly enhanced by NC (20 and 200µM applied sequentially) but not affected by cuprizone. The facilitating effect, which was blocked by suramin and reversible after washout of the drug, did not occur following administration of neocuproine-copper(I) complex (NC-Cu). NC (20µM) significantly increased the second, more sustained contraction; whereas 200µM decreased this response. These effects of NC on the sustained contractions were not elicited by NC-Cu and not blocked by suramin. Nitric oxide synthase inhibitor, L-nitroarginine, did not alter the responses to NC. NC (20µM) elicited a marked increase in basal tone of the strips. This effect was less prominent after the second application of 200µM NC or with NC-Cu treatment or in the presence of suramin. In anesthetized rats, during continous infusion cystometry, intravesical infusion of 50µM NC but not NC-Cu or cuprizone, significantly decreased the intercontraction interval (ICI) without changing contraction amplitude. The ICI returned to normal after washout of NC. Suramin blocked this effect. These results indicate that NC enhances bladder activity by facilitating purinergic excitatory responses and that copper(I)-sensitive mechanisms tonically inhibit purinergic transmission in the bladder.

Key words: Bladder, Copper, Neocuproine, Nerve-evoked contractions, Purinergic activity, Voiding function

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