Neocuproine, a Copper (I) Chelator, Potentiates Purinergic Component of Vas Deferens Contractions Elicited by Electrical Field Stimulation

Abstract

Effects of the specific copper (I) chelator, neocuproine, on the purinergic and adrenergic components of nerve-evoked contractions were investigated in the prostatic rat vas deferens. Electrical field stimulation (EFS; 4 Hz) induced bimodal contractions of vas deferens tissue in the presence of α₁-adrenoceptor antagonist prazosin (to isolate the purinergic component) or purinoceptor antagonist suramin (to isolate the adrenergic component). Neocuproine significantly potentiated the purinergic component of the contractile responses to EFS. However, the same agent failed to elicit any significant effect on the adrenergic component of nerve-evoked contractions. The copper (II) chelator cuprizone could not affect the purinergic component of contractions. The potentiating effect of neocuproine which was reversible after washout of the drug, did not occur following the application of the pre-prepared neocuproine-copper (I) complex. A nitric oxide synthase inhibitor, L-nitroarginine; a cyclooxygenase inhibitor, indomethacin or an α₂-adrenoceptor antagonist, yohimbine, failed to alter the responses to neocuproine on the purinergic component of the contraction to EFS. Neocuproine did not elicit any significant effect on preparations in which the purinergic receptors were desensitized with α,β-methylene ATP. In conclusion, our results suggest that neocuproine potentiates the purinergic component of rat vas deferens contractions elicited by EFS, presumably by facilitating purinergic neurotransmission and that copper (I)-sensitive mechanisms can modulate purinergic transmission in this tissue.

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

“…Decrease on the SC-induced by NC but not cuprizone indicated that a copper(I)-sensitive mechanism may play a role in the inhibitor effect of NC in the mouse bladder. The activity/inactivity of copper chelators are in agreement with our previous studies conducted on rat bladder and vas deferens (17,19). However in the rat urinary bladder, L-NOARG, a nitric oxide synthase inhibitor, had no effect on the facilitator effect of NC on nerve-evoked contractions.…”

“…Our previous studies showed that the chelation of endogenous copper(I) caused an enhancement on the spontaneous activity in some of rat tissues such as bladder and vas deferens tissues of rats and pregnant rat myometrium (16)(17)(18)(19) and the involvement of purinergic receptors and/or Ca 2+ levels in those responses. In the present study, our aim was to evaluate whether the contribution of purinergic pathways and/or intracellular calcium levels in the effects of neocuproine in the mouse bladder tissues are similar to rat tissues or not.…”

Differential effects elicited by neocuproine, a copper (1) chelator, on the bladder activity in mouse and rat

“…The excitatory effect was significantly inhibited by suramin, a purinergic receptor antagonist. These results are consistent with the previous studies in rat bladder and vas deferens tissues and the results have been suggested that NC-induced excitatory effects may be owing to the activation of the purinergic excitatory responses (Gocmen et al, 2004(Gocmen et al, , 2005. In contrast to the response of rat bladder, NC caused recurrent and reversible inhibition on spontaneous contractions and basal tonus on in vitro isolated mouse bladder strips and whole bladder tissue.…”

“…The inhibitor effect did not occur in the presence of pre-prepared NC-Cu(I) complex. The results indicate that a copper (I)-sensitive mechanism may play a role in the inhibition effect of NC on purinergic responses of mouse bladder tissue, and previous studies of Gocmen et al, 2004 and support that the copper(1)-sensitive mechanism may play a role by facilitating purinergic excitatory response (Gocmen et al, 2004(Gocmen et al, , 2005. In addition, it has been suggested that NO releases with S-nitrosothiols, a sulfhydryl-containing compound, and NC affect the responses of S-nitrosothiols by its ability to chelate copper in the bladder (De Man et al, 1999), however, it was exhibited that it is different from L-NOARG mechanism, because of that NOS inhibitor, L-NOARG did not change the effect of NC responses (Gocmen et al, 2004).…”

“…It is well known that Neocuproine (NC) enhances bladder and vas deferens activity by facilitating purinergic excitatory responses (Gocmen et al, 2004(Gocmen et al, , 2005. NC can also inhibit the relaxation of electrically stimulated mouse corpus cavernosum (Gocmen et al, 2000).…”