Advances in the pharmacological control of the bladder

Andersson, Karl‐Erik

doi:10.1111/j.1469-445x.1999.tb00083.x

Cited by 120 publications

(77 citation statements)

References 71 publications

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“…It is reported that antimuscarinic drugs act mainly during the storage phase, increasing bladder capacity and decreasing urge (11); and during the storage phase, there is normally no activity in parasympathetic nerves (12). However, if there is an increased non-neuronal ACh release during storage, which is proposed to be a contributing factor to OAB, it is possible that antimuscarinic drugs have some inhibitory effects on muscarinic receptors activated by the non-neuronal ACh.…”

Section: Clinical Significance Of Non-neuronal Ach From Bladder Urothmentioning

confidence: 99%

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Basic and Clinical Aspects of Non-neuronal Acetylcholine: Expression of Non-neuronal Acetylcholine in Urothelium and Its Clinical Significance

et al. 2008

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Abstract.Recently, several reports demonstrate that non-neuronal acetylcholine (ACh) release may contribute to various pathophysiological conditions. In this review, we presented our experiments designed to evaluate the non-neuronal cholinergic system in human bladder. After insertion of the microdialysis probe, human bladder strips were suspended in an organ bath filled with Krebs-Henseleit solution, and Ringer solution was perfused into the probe. ACh release was measured by microdialysis and HPLC. The contribution of urothelium and the effects of age and stretch of bladder strips on non-neuronal ACh release were evaluated. Choline acetyltransferase (ChAT) immunohistochemical staining of bladder was also performed. Immunohistochemistry showed marked ChAT-positive staining in the urothelium. There was tetrodotoxininsensitive non-neuronal ACh release and this was significantly higher in strips with urothelium than in strips without urothelium. The non-neuronal ACh release was increased with age. Stretch of bladder strips caused increases in non-neuronal ACh release. The stretch-induced release of non-neuronal ACh was increased with age. Our data demonstrate that there is a non-neuronal cholinergic system in human bladder and that urothelium contributes to non-neuronal ACh release. There was significant age-related and stretch-induced increase in non-neuronal ACh release. It is suggested that the non-neuronal cholinergic system may contribute to the physiology and pathophysiology of human bladder. We also discussed the clinical significance of the nonneuronal cholinergic system in human bladder.

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Section: Clinical Significance Of Non-neuronal Ach From Bladder Urothmentioning

confidence: 99%

“…Antimuscarinic drugs are usually used for treatment of OAB (10). Symptoms of OAB usually occur during the storage phase, and antimuscarinic drugs act mainly during this cycle, increasing bladder capacity and decreasing urge (11). However, during the storage phase, there is normally no activity in parasympathetic nerves (12).…”

Section: Introductionmentioning

confidence: 99%

Basic and Clinical Aspects of Non-neuronal Acetylcholine: Expression of Non-neuronal Acetylcholine in Urothelium and Its Clinical Significance

et al. 2008

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“…When there is no defined cause, the term "idiopathic detrusor overactivity" is used. When there is an associated relevant neurological condition, such as multiple sclerosis, cerebrovascular accidents, spinal cord injuries, and Parkinson's disease, the recommended term is "neurogenic detrusor overactivity" (1,2,3).…”

mentioning

confidence: 99%

Increased connexin43-mediated intercellular communication in a rat model of bladder overactivity in vivo

Christ

Day²,

Day³

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

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101

111

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Bladder overactivity associated with outflow obstruction is a common human condition recapitulated in the female rat by narrowing the diameter of the urethra. The goal of these studies was to evaluate the role of intercellular communication through connexin43 (Cx43)-derived gap junction channels to bladder overactivity following partial urethral outflow obstruction of 3-day to 6-wk duration. Cx43 mRNA and protein expression were barely detectable by Northern or Western blots, respectively, in the detrusor layer of normal bladders, but bands were found with both techniques after 6 wk of obstruction. Linear regression analysis of the RT-PCR data revealed a statistically significant positive correlation between the duration of obstruction (again, ranging from 3-day to 6-wk duration) and Cx43 mRNA transcript levels, such that after 6 wk of obstruction, Cx43 transcript levels were ≈15-fold greater than initial control values. When taking into account the approximately fivefold increase in bladder weight over this same time frame, the absolute amount of Cx43 mRNA in the bladder apparently increased by ≈75-fold. In that regard, as anticipated, and consistent with previous observations, 6 wk of obstruction was also associated with a significant increase in spontaneous bladder contractions between micturitions. The amplitude of these contractions was significantly reduced by heptanol given intravesically. Furthermore, carbachol-precontracted bladder strips from obstructed animals were more sensitive to heptanol-induced relaxation (100 μM) than their unobstructed counterparts ( n = 6; P < 0.01). When bladder strips were equivalently precontracted via electrical field stimulation (EFS; 20 Hz), similar heptanol-induced relaxation responses were observed. However, the tetrodotoxin-resistant portion of the EFS-induced contraction was greater in the obstructed than in the unobstructed animals, and this portion of the contractile response was more sensitive to heptanol-induced relaxation in obstructed than unobstructed bladders ( n = 7; P < 0.01). Taken together, these observations indicate that partial outlet obstruction produces an overactive bladder that may be more dependent on intercellular communication through gap junctions for modulation of contractile responses than its normal counterpart.

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“…The mid portion of the bladder body that did not contain urothelium was taken out and used for the real-time polymerase chain reaction (RT-PCR) procedure. 2 and M 3 receptor messenger RNAs). Muscarinic M 2 and M 3 receptor messenger RNAs (mRNAs) in the experimental bladder dome were measured using a RT-PCR method.…”

mentioning

confidence: 99%

“…Five microliters of the mixture was used for RT-PCR, which was carried out using a LightCycler thermal cycler system with a LightCycler-FastStart DNA Master Hybridization Probe (Roche Diagnosthe vesical pressure during voiding and bladder capacity in vivo (7,12,14,19). The urinary bladder is very rich in muscarinic receptors of the M 2 and M 3 subtypes and they play a role in the contraction of the detrusor muscle (2). In a report by Shapiro, it was shown that ERT decreases the detrusor muscarinic receptor in ovariectomized rats (17).…”

mentioning

confidence: 99%

Effects of long-term estradiol treatment on the contractile response to muscarine and muscarinic receptor subtypes in the bladder of aged female rats

2007

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In this study, we tried to elucidate the effect of estrogen treatment on the detrusor contractile response to muscarine and muscarine receptor subtypes of the bladder in 13-month-old female Wistar rats. The rats were divided into two groups, controls and rats treated with estradiol for 12 weeks. After the treatment phase, we monitored micturition behavior in addition to performing cystometrograms after the administration of muscarine, and real-time polymerase chain reaction for mRNA expression of the muscarinic receptor subtypes in the detrusor muscle. Our data indicated that there was a significant increase in the maximum micturition volume in the estradioltreated rats. The urodynamic results indicated significant changes in the maximum detrusor pressure following the administration of muscarine in the estradiol-treated rats, in contrast to the controls for which no significant changes were observed. Furthermore, M 3 receptor mRNAs in the detrusor muscle were significantly decreased in the estradiol-treated rats as compared to the control rats, while there were no differences noted for the M 2 receptor mRNAs. Our data demonstrates that long-term estradiol treatment might be capable of increasing the potential detrusor contractility, and thus, estradiol might be a therapeutic agent that can be used to target the M 3 receptors during the treatment of detrusor instability.The most common type of urinary incontinence is stress urinary incontinence, which is defined as "the involuntary leakage on effort or exertion, or on sneezing or coughing." Its prevalence rate in women ranges from 6.4% to 35% (9, 10). Urge incontinence is defined as "involuntary leakage of urine that is associated with a sudden, strong desire to void", whereas mixed incontinence is regarded as "a combination of both urge and stress incontinence". Studies have shown that both mixed and urge incontinence increases steadily with age. Thus, urinary incontinence is a common disease in elderly women with physical and/or psychosocial implications.Clinical observations suggest that menopause contributes significantly to the onset of female urinary incontinence. One of the conservative therapies used to treat mixed urinary incontinence in women is estrogen replacement therapy (ERT). While alterations in female sex hormones appear to play a major role in mediating bladder dysfunction, the use of ERT in the management of post-menopausal urinary incontinence still remains controversial. A meta-analysis study reported there was a significant ERT effect on the subjective improvement of stress incontinence (6). However, in contrast to this, a more recent report has indicated that ERT worsened the characteristics of incontinence among symptomatic women (8).Previous investigations have shown that ovariectomy decreased the detrusor muscle response to cholinergic agents in vitro, and that ERT increased

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Advances in the pharmacological control of the bladder

Cited by 120 publications

References 71 publications

Basic and Clinical Aspects of Non-neuronal Acetylcholine: Expression of Non-neuronal Acetylcholine in Urothelium and Its Clinical Significance

Basic and Clinical Aspects of Non-neuronal Acetylcholine: Expression of Non-neuronal Acetylcholine in Urothelium and Its Clinical Significance

Increased connexin43-mediated intercellular communication in a rat model of bladder overactivity in vivo

Effects of long-term estradiol treatment on the contractile response to muscarine and muscarinic receptor subtypes in the bladder of aged female rats

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