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

PubMedID: 15501992The 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 induced bimodal contractions of bladder strips. An initial, transient contraction that was blocked by the purinergic antagonist, suramin, was significantly enhanced by NC (20 and 200 µM 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 (20 µM) significantly increased the second, more sustained contraction, whereas 200 µM decreased this response. These effects of NC on the sustained contractions were not elicited by NC-Cu and not blocked by suramin. The nitric oxide synthase inhibitor, L-nitroarginine, did not alter the responses to NC. NC (20 µM) elicited a marked increase in basal tone of the strips. This effect was less prominent after the second application of 200 µM NC or with NC-Cu treatment or in the presence of suramin. In anesthetized rats, during continuous infusion cystometry, intravesical infusion of 50 µM 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. Copyright © 2005 by The American Society for Pharmacology and Experimental Therapeutics

Prejunctional facilitatory effect of a thiol-alkylating agent N-Ethylmaleimide on neurogenic contractions in rat prostate smooth muscle

PubMedID: 22275139Aims The effect of a non-specific thiol-alkylating agent N-ethylmaleimide (NEM) was studied on neurogenic contractile mechanisms in rat ventral prostate gland. Methods Male Wistar albino rats were used. The rats were killed by cervical dislocation under sevoflurane anesthesia and ventral prostate gland was removed. Two preparations were obtained from each lobe. Neurally evoked isometric contractions were induced using trains of electrical field stimulation (EFS; 0.5, 1, 4, or 8Hz). The effect of NEM on the contractions to EFS was examined in the absence or presence of adrenergic and/or purinergic antagonists. Results NEM enhanced the EFS-evoked contractions without altering the basal tone. These effects were significantly suppressed by an ? 1- adrenergic receptor antagonist (prazosin), a P2-purinergic antagonist (suramin), a specific P2X-receptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'- disulfonate (PPADS), an ATP analog (?,ß-methylene ATP), or a calcium channel blocker (verapamil). This facilitating effect of NEM did not occur following the administration of L-cysteine or glutathione which saturated NEM with excess thiols. However, a thiol-oxidant diamide failed to affect the contractions to EFS. An adrenergic neuron blocker (guanethidine) completely suppressed the responses to NEM. On the other hand, an ? 2- adrenergic receptor blocker (yohimbine), a nitric oxide synthase inhibitor (N ?-nitro-L-arginine) or a cholinergic muscarinic receptor antagonist (atropine) did not significantly affect the facilitatory response of NEM. Conclusions These findings suggest that NEM has a prejunctional facilitatory action on the adrenergic nerves in rat prostate tissue to enhance release of transmitters, noradrenaline, and ATP. NEM sensitive proteins involved in transmitter release mechanisms can play a role in this effect. Copyright © 2012 Wiley Periodicals, Inc