| 18223671 |
Hernandez M, Barahona MV, Recio P, Navarro-Dorado J, Bustamante S, Benedito S, Garcia-Sacristan A, Prieto D, Orensanz LM: Role of neuronal voltage-gated K (+) channels in the modulation of the nitrergic neurotransmission of the pig urinary bladder neck. Br J Pharmacol. 2008 Mar;153(6):1251-8. Epub 2008 Jan 28.
BACKGROUND AND PURPOSE: As nitric oxide (NO) plays an essential role in the inhibitory neurotransmission of the bladder neck of several species, the current study investigates the mechanisms underlying the NO-induced relaxations in the pig urinary bladder neck. EXPERIMENTAL APPROACH: Urothelium-denuded bladder neck strips were dissected and mounted in isolated organ baths containing a physiological saline solution at 37 degrees C and continuously gassed with 5% CO (2) and 95% O (2), for isometric force recording. The relaxations to transmural nerve stimulation (EFS), or to exogenously applied acidified NaNO (2) solution were carried out on strips pre-contracted with phenylephrine, and treated with guanethidine and atropine, to block noradrenergic neurotransmission and muscarinic receptors, respectively. KEY RESULTS: EFS (0.2-1 Hz) and addition of acidified NaNO (2) solution (1 microM-1 mM) evoked frequency- and concentration-dependent relaxations, respectively. These responses were potently reduced by the blockade of guanylate cyclase and were not modified by the K (+) channel blockers iberiotoxin, charybdotoxin, apamin or glibenclamide. The voltage-gated K (+) (Kv) channels inhibitor 4-aminopyridine, greatly enhanced the nitrergic relaxations evoked by EFS, but did not affect the NaNO (2) solution-induced relaxations. CONCLUSIONS AND IMPLICATIONS: NO, whose release is modulated by pre-junctional Kv channels, relaxes the pig urinary bladder neck through a mechanism dependent on the activation of guanylate cyclase, in which post-junctional K (+) channels do not seem to be involved. Modulation of Kv channels could be useful in the therapy of the urinary incontinence produced by intrinsic sphincteric deficiency. |
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