Endogenous Hydrogen Sulfide has a Powerful Role in Inhibitory Neurotransmission to the Pig Bladder Neck

Fernandes, Vítor S.; Ribeiro, Ana S. F.; Martínez, María Pilar; Orensanz, Luis M.; Barahona, María Victoria; Martínez‐Sáenz, Ana; Recio, Paz; Benedito, Sara; Bustamante, Salvador; Carballido, Joaquı́n; García‐Sacristán, Albino; Prieto, Dolores; Hernández, Medardo

doi:10.1016/j.juro.2012.10.006

Cited by 29 publications

(35 citation statements)

References 27 publications

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“…Western blot assays showed a band compatible with that expected for CSE in the muscular layer, and immunostaining of ureteral samples revealed a labeling for CSE protein within nerve fibers widely distributed among smooth muscle bundles. The high density and the distribution of CSE immunoreactivity observed in the intravesical ureter agree with that found in pig bladder neck [12]. In the current study, the existence of CSE-immunoreactive elements around small arteries also suggests a role for H 2 S in the regulation of intravesical ureter blood flow, thus supporting an important role for H 2 S in vascular tone modulation [22].…”

Section: Discussionsupporting

confidence: 89%

“…Observations were made with a fluorescence microscope (Olympus IX51). No immunoreactivity could be detected in sections incubated in the absence of the primary antiserum [12].…”

Section: Methodsmentioning

confidence: 90%

“…The bath solution was then changed every 15 min for a period of 90 min, the preparations were incubated with the specific treatments for 30 min, and then a second relaxation curve was constructed. The concentration of the agents used was chosen on the basis of previous studies [11],[12]. Control curves were run in parallel.…”

Section: Methodsmentioning

confidence: 99%

“…Thus, in rat bladder detrusor, the H 2 S donor NaHS induces contraction via stimulation of capsaicin-sensitive primary afferents (CSPA), leading to release of tachykinins, such as substance P or neurokinin A [9],[10] whereas in bladder outflow region H 2 S produces smooth muscle relaxation. In fact, in the pig bladder neck, H 2 S, synthesized by CSE, acts as a signaling molecule in the inhibitory neurotransmission, producing smooth muscle relaxation via K ATP channel activation and favouring the release of the sensory neuropeptides [11],[12].…”

Section: Introductionmentioning

confidence: 99%

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Hydrogen Sulfide Plays a Key Role in the Inhibitory Neurotransmission to the Pig Intravesical Ureter

et al. 2014

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According to previous observations nitric oxide (NO), as well as an unknown nature mediator are involved in the inhibitory neurotransmission to the intravesical ureter. This study investigates the hydrogen sulfide (H2S) role in the neurogenic relaxation of the pig intravesical ureter. We have performed western blot and immunohistochemistry to study the expression of the H2S synthesis enzymes cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS), measurement of enzymatic production of H2S and myographic studies for isometric force recording. Immunohistochemical assays showed a high CSE expression in the intravesical ureter muscular layer, as well as a strong CSE-immunoreactivity within nerve fibres distributed along smooth muscle bundles. CBS expression, however, was not consistently observed. On ureteral strips precontracted with thromboxane A2 analogue U46619, electrical field stimulation (EFS) and the H2S donor P-(4-methoxyphenyl)-P-4-morpholinylphosphinodithioic acid (GYY4137) evoked frequency- and concentration-dependent relaxations. CSE inhibition with DL-propargylglycine (PPG) reduced EFS-elicited responses and a combined blockade of both CSE and NO synthase (NOS) with, respectively, PPG and NG-nitro-L-arginine (L-NOARG), greatly reduced such relaxations. Endogenous H2S production rate was reduced by PPG, rescued by addition of GYY4137 and was not changed by L-NOARG. EFS and GYY4137 relaxations were also reduced by capsaicin-sensitive primary afferents (CSPA) desensitization with capsaicin and blockade of ATP-dependent K+ (KATP) channels, transient receptor potential A1 (TRPA1), transient receptor potential vanilloid 1 (TRPV1), vasoactive intestinal peptide/pituitary adenylyl cyclase-activating polypeptide (VIP/PACAP) and calcitonin gene-related peptide (CGRP) receptors with glibenclamide, HC030031, AMG9810, PACAP6–38 and CGRP8–37, respectively. These results suggest that H2S, synthesized by CSE, is involved in the inhibitory neurotransmission to the pig intravesical ureter, through an NO-independent pathway, producing smooth muscle relaxation via KATP channel activation. H2S also promotes the release of inhibitory neuropeptides, as PACAP 38 and/or CGRP from CSPA through TRPA1, TRPV1 and related ion channel activation.

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Section: Discussionsupporting

confidence: 89%

“…Observations were made with a fluorescence microscope (Olympus IX51). No immunoreactivity could be detected in sections incubated in the absence of the primary antiserum [12].…”

Section: Methodsmentioning

confidence: 90%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hydrogen Sulfide Plays a Key Role in the Inhibitory Neurotransmission to the Pig Intravesical Ureter

et al. 2014

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“…These studies provided also evidence for a role of endogenous H 2 S released from nerves involvement in the inhibitory transmission of the outflow region (Fernandes et al 2013a). Additionally, H 2 S promotes the release of inhibitory neuropeptide by the activation of TRPA1 and TRPV1 (Fernandes et al 2013b). Therefore, at the present stage, K ATP channels, TRPA1, and TRPV1 are considered feasible targets for H 2 S in the bladder function.…”

Section: Animal Studiesmentioning

confidence: 70%

Hydrogen Sulfide and Urogenital Tract

Bianca

Cirino

Sorrentino

2015

Chemistry, Biochemistry and Pharmacology of Hydrogen Sulfide

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In this chapter the role played by H2S in the physiopathology of urogenital tract revising animal and human data available in the current relevant literature is discussed. H2S pathway has been demonstrated to be involved in the mechanism underlying penile erection in human and experimental animal. Both cystathionine-β synthase (CBS) and cystathionine-γ lyase (CSE) are expressed in the human corpus cavernosum and exogenous H2S relaxes isolated human corpus cavernosum strips in an endothelium-independent manner. Hydrogen sulfide pathway also accounts for the direct vasodilatory effect operated by testosterone on isolated vessels. Convincing evidence suggests that H2S can influence the cGMP pathway by inhibiting the phosphodiesterase 5 (PDE-5) activity. All these findings taken together suggest an important role for the H2S pathway in human corpus cavernosum homeostasis. However, H2S effect is not confined to human corpus cavernosum but also plays an important role in human bladder. Human bladder expresses mainly CBS and generates in vitro detectable amount of H2S. In addition the bladder relaxant effect of the PDE-5 inhibitor sildenafil involves H2S as mediator. In conclusion the H2S pathway is not only involved in penile erection but also plays a role in bladder homeostasis. In addition the finding that it involved in the mechanism of action of PDE-5 inhibitors strongly suggests that modulation of this pathway can represent a therapeutic target for the treatment of erectile dysfunction and bladder diseases.

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Neuronal and non-neuronal bradykinin receptors are involved in the contraction and/or relaxation to the pig bladder neck smooth muscle

Ribeiro

Fernandes

Martínez

et al. 2013

Neurourol. Urodynam.

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These results suggest that BK produces contraction of pig bladder neck via smooth muscle B2 receptors coupled to extracellular Ca(2+) entry via VOC and non-VOC channels with a minor role for intracellular Ca(2+) mobilization. Facilitatory neuronal B2 receptors modulating NANC inhibitory neurotransmission and urothelial B1 receptors producing relaxation via the COX-1 pathway and BKCa channel opening are also demonstrated. Neurourol. Urodynam. 33:558-565, 2014. © 2013 Wiley Periodicals, Inc.

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Endogenous Hydrogen Sulfide has a Powerful Role in Inhibitory Neurotransmission to the Pig Bladder Neck

Abstract: Results suggest that endogenous H2S synthesized by cystathionine γ-lyase and released from intramural nerves acts as a powerful signaling molecule in nitric oxide independent inhibitory transmission to the pig bladder neck.

Cited by 29 publications

References 27 publications

Hydrogen Sulfide Plays a Key Role in the Inhibitory Neurotransmission to the Pig Intravesical Ureter

Hydrogen Sulfide Plays a Key Role in the Inhibitory Neurotransmission to the Pig Intravesical Ureter

Hydrogen Sulfide and Urogenital Tract

Neuronal and non-neuronal bradykinin receptors are involved in the contraction and/or relaxation to the pig bladder neck smooth muscle

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