Nitric Oxide/Cyclic Guanosine Monophosphate Signalling Mediates an Inhibitory Action on Sensory Pathways of the Micturition Reflex in the Rat

Caremel, R.; Oger-Roussel, Stéphanie; Behr‐Roussel, Delphine; Grise, P.; Giuliano, François

doi:10.1016/j.eururo.2010.07.026

Cited by 55 publications

(43 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…One such inhibitor, L-NAME, increased the afferent response to bladder filling by ϳ50%, which was reversed by activation of NO pathways with L-arginine. Thus NO seems to be able to inhibit afferent activity, an observation consistent with earlier cystometric analysis of the effect of activating and inhibiting the NO pathway (59,225,236). Taken together, these findings suggest that alterations in NO levels may have a role in the modulation of urothelial signaling.…”

Section: Nosupporting

confidence: 76%

Urothelial Signaling

Birder

Andersson

2013

Physiological Reviews

390

362

View full text Add to dashboard Cite

The urothelium, which lines the inner surface of the renal pelvis, the ureters, and the urinary bladder, not only forms a high-resistance barrier to ion, solute and water flux, and pathogens, but also functions as an integral part of a sensory web which receives, amplifies, and transmits information about its external milieu. Urothelial cells have the ability to sense changes in their extracellular environment, and respond to chemical, mechanical and thermal stimuli by releasing various factors such as ATP, nitric oxide, and acetylcholine. They express a variety of receptors and ion channels, including P2X3 purinergic receptors, nicotinic and muscarinic receptors, and TRP channels, which all have been implicated in urothelial-neuronal interactions, and involved in signals that via components in the underlying lamina propria, such as interstitial cells, can be amplified and conveyed to nerves, detrusor muscle cells, and ultimately the central nervous system. The specialized anatomy of the urothelium and underlying structures, and the possible communication mechanisms from urothelial cells to various cell types within the bladder wall are described. Changes in the urothelium/ lamina propria ("mucosa") produced by different bladder disorders are discussed, as well as the mucosa as a target for therapeutic interventions.

show abstract

Section: Nosupporting

confidence: 76%

Urothelial Signaling

Birder

Andersson

2013

Physiological Reviews

390

362

View full text Add to dashboard Cite

show abstract

“…In functional support, PRKG1-deficient mice showed bladder hyperactivity with reduced bladder capacity and micturition volumes (Persson et al 2000). There is increasing evidence that NO-cGMP signaling also controls sensory pathways of the micturition reflex (Caremel et al 2010) and is active in interstitial cells to modulate phasic contractile activity (Lagou et al 2006). Our findings demonstrating predominant expression levels and agonist-induced activity of GC-A (compared with GC-B) suggest additional local roles mainly for ANP-cGMP signaling.…”

Section: Organ-specific Characteristics Of Cgmp Signalingmentioning

confidence: 66%

“…Local roles for cGMP signaling comprise the regulation of muscle contractions and micturition sensations in the bladder (Persson et al 2000, Andersson & Arner 2004, Sandner et al 2009, Caremel et al 2010, the relaxation of stromal smooth muscle and control of cell proliferation in the prostate (Gradini et al 1999, Sandner et al 2009, Fibbi et al 2010, Zenzmaier et al 2010, and regulation of peristalsis and secretory epithelial cell functions in the epididymis (Mewe et al 2006, Shum et al 2008. Although certain factors implicated in cGMP pathways have been demonstrated by immunohistochemical, RT-PCR, and functional approaches, the cGMP signaling system in these organs is still poorly characterized.…”

Section: Introductionmentioning

confidence: 99%

Cyclic GMP signaling in rat urinary bladder, prostate, and epididymis: tissue-specific changes with aging and in response to Leydig cell depletion

Müller

Mukhopadhyay²,

Davidoff³

et al. 2011

Reproduction

View full text Add to dashboard Cite

Aging of the male reproductive system leads to changes in endocrine signaling and is frequently associated with the emergence of prostate hyperplasia and bladder dysfunctions. Recent reports highlight prostate and bladder as promising targets for therapeutic interventions with inhibitors of the cyclic GMP (cGMP)-degrading phosphodiesterase 5 (PDE5). However, the cGMP signaling system in these organs is as yet poorly characterized, and the possibility of age-related alterations has not been addressed. This study investigates key proteins of cGMP pathways in bladder, prostate, and epididymis of young (3 months) and old (23-24 months) Wistar rats. Local differences in the abundance of PDE5, soluble guanylyl cyclase (sGC) and particulate guanylyl cyclases (GC-A, GC-B), endothelial nitric oxide synthase, and cGMP-dependent protein kinase I (PRKG1 (cGKI)) revealed pronounced tissue-specific peculiarities. Although cGMP-generating enzymes were not affected by age in all organs, we recognized age-related decreases of PDE5 expression in bladder and a selective diminishment of membrane-associated PRKG1 in epididymis. In disagreement with published data, all cGMP pathway proteins including PDE5 are poorly expressed in prostate. However, prostatic PRKG1 expression increases with aging. Androgen withdrawal during temporary Leydig cell elimination induced a massive (O12-fold) upregulation of PRKG1 in prostate but not in other (penis and epididymis) androgen-dependent organs. These findings identify PRKG1 as a key androgen-sensitive signaling protein in prostate of possible importance for growth regulation. The elucidated effects may have significance for age-associated pathologies in the male lower-urinary tract.

show abstract

“…PDE-5 inhibitors increase the intracellular concentration of cGMP, therefore augmenting the NO effects. Regarding the role of NO in regulation the neuronal pathways of voiding function [13,14], PDE-5 inhibitors could improve the storage and urination function due to interfering action with non-functional contractions of a neurogenic bladder. Their beneficial outcomes in benign prostatic hyperplasia are previously observed [11,12].…”

Section: Discussionmentioning

confidence: 99%

“…Mechanism of action of sildenafil on bladder muscles has been investigated [12]. Nitric oxide (NO), the pathway which PDE-5 inhibitors reinforce, regulates the urination reflex through modulation of afferent nerve routes [13].…”

Section: Introductionmentioning

confidence: 99%

Renal function in a rat model of neurogenic bladder, effect of statins and phosphodiesterase-5 inhibitors

Mirzaii‐Dizgah

Salmanyan

2013

Eur Spine J

View full text Add to dashboard Cite

Purpose Neurogenic bladder is a common complication of several central nervous system injuries. Statins and phosphodiesterase-5 (PDE-5) inhibitors are reportedly beneficial in neural injuries and urinary system dysfunction. The effect of simvastatin, sildenafil and tadalafil on several renal function indices of an animal model of neurogenic bladder was investigated. Methods Forty male rats were assessed in five equal groups. Dura mater and the cord were injured with an aneurysmal clamp at the level of T9-T10 in all rats except in sham group. The sham and control groups (treated by normal saline), simvastatin (4 mg/kg), sildenafil (5 mg/kg), and tadalafil (2 mg/kg) groups received treatment (i.p.) for seven consecutive days following injury. Renal system and motor functions were assessed at day 28 following injury. Data were analyzed by analysis of variance followed by the Student-Newman-Keuls post hoc test. Results Simvastatin improved both the renal and the motor function compared with the control group. However, sildenafil and tadalafil could only improve the motor function but could not make any significant differences in renal indices in comparison with the control group. Conclusion Statins can effectively improve the motor and renal functions in a condition of renal dysfunction in a rat model of neurogenic bladder. PDE-5 inhibitors could help to improve motor function, but are not helpful in renal function, at least in short time.

show abstract

Nitric Oxide/Cyclic Guanosine Monophosphate Signalling Mediates an Inhibitory Action on Sensory Pathways of the Micturition Reflex in the Rat

Cited by 55 publications

References 28 publications

Urothelial Signaling

Urothelial Signaling

Cyclic GMP signaling in rat urinary bladder, prostate, and epididymis: tissue-specific changes with aging and in response to Leydig cell depletion

Renal function in a rat model of neurogenic bladder, effect of statins and phosphodiesterase-5 inhibitors

Contact Info

Product

Resources

About