A Quantitative Study of Atropine-Resistant Contractile Responses in Human Detrusor Smooth Muscle, From Stable, Unstable and Obstructed Bladders

Bayliss, Mark; Wu, Changhao; Newgreen, Donald; Mundy, Anthony R.; Fry, Christopher

doi:10.1097/00005392-199911000-00079

Cited by 62 publications

(79 citation statements)

References 25 publications

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“…In healthy human bladder, the purinergic component is minor but is increased in obstruction (Bayliss et al, 1999), similar to the rabbit (Calvert et al, 2001). In the present study of guinea pigs, the relative contributions of the cholinergic and purinergic components did not change between control, sham and obstructed bladders.…”

Section: Efs and Effect Of Cholinergic Agonists In Obstructionsupporting

confidence: 52%

Conscious voiding during bladder obstruction in guinea pigs correlates with contractile activity of isolated bladders

Nicholas

Keightley

Brookes

et al. 2015

Autonomic Neuroscience

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Purpose: There are many hypotheses accounting for detrusor overactivity, however the exact mechanisms are still incompletely understood. We used a model of bladder outlet obstruction in male guinea pigs as a way to produce detrusor overactivity. The objective was to determine whether changes in voiding of obstructed guinea pigs correlates with specific changes in contractile activity of their isolated bladders in vitro. Material and methods: Conscious voiding activity of sham-operated and obstructed animals was measured in metabolic cages. Contractile activity (spontaneous or evoked by distension, electrical field stimulation or cholinergic agonists) was recorded via a pressure transducer in the isolated bladders in vitro. Results: The frequency of conscious voiding increased (while voiding volume decreased) in the obstructed group, compared with the sham-operated group, 4 weeks after surgical intervention. In comparison to the sham-operated animals, the bladders from the obstructed guinea pigs were enlarged and inflamed, their frequency of spontaneous contractions was higher, while the amplitudes of electrical field stimulation (EFS)-induced contractions and bladder compliance were lower. Changes in conscious voiding during obstruction were significantly associated with alterations in structural parameters (bladder weight, thickness and histological damage score) and functional contractile parameters (frequency of spontaneous contractions, amplitude of EFS-induced contractions and bladder compliance) of their isolated bladders. Conclusions: Our findings revealed significant association between conscious voiding and structural and contractile activity changes of the isolated bladders in obstruction. The data suggest that change in contractile activity of the bladder itself is a major contributor to obstruction-induced bladder overactivity.

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Section: Efs and Effect Of Cholinergic Agonists In Obstructionsupporting

confidence: 52%

Conscious voiding during bladder obstruction in guinea pigs correlates with contractile activity of isolated bladders

Nicholas

Keightley

Brookes

et al. 2015

Autonomic Neuroscience

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“…63 ATP has also been implicated as a neurotransmitter in the generation of unstable contractions in idiopathic detrusor overactivity. [67][68][69] Animal studies of bladder strips from guinea pigs 70 and rats 71 indicate that BTX-A inhibits the release of both acetylcholine and ATP, providing a rationale for its possible use in treating patients with idiopathic detrusor overactivity.…”

Section: Effects On Acetylcholine and Atp Releasementioning

confidence: 99%

Drug Insight: biological effects of botulinum toxin A in the lower urinary tract

et al. 2008

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SUMMARYBotulinum toxins can effectively and selectively disrupt and modulate neurotransmission in striated muscle. Recently, urologists have become interested in the use of these toxins in patients with detrusor overactivity and other urological disorders. In both striated and smooth muscle, botulinum toxin A (BTX-A) is internalized by presynaptic neurons after binding to an extracellular receptor (ganglioside and presumably synaptic vesicle protein 2C). In the neuronal cytosol, BTX-A disrupts fusion of the acetylcholine-containing vesicle with the neuronal wall by cleaving the SNAP-25 protein in the synaptic fusion complex. The net effect is selective paralysis of the low-grade contractions of the unstable detrusor, while still allowing high-grade contraction that initiates micturition. Additionally, BTX-A seems to have effects on afferent nerve activity by modulating the release of ATP in the urothelium, blocking the release of substance P, calcitonin gene-related peptide and glutamate from afferent nerves, and reducing levels of nerve growth factor. These effects on sensory feedback loops might not only help to explain the mechanism of BTX-A in relieving symptoms of overactive bladder, but also suggest a potential role for BTX-A in the relief of hyperalgesia associated with lower urinary tract disorders.

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“…EctoATPases would ensure rapid breakdown of ATP and prevent activation of the extra-junctional receptors. In overactive bladders a purinoceptor responses is occasionally seen, 61 suggesting that ATP can now reach the receptors.…”

Section: Sexual and Lut Function Af Brading Et Almentioning

confidence: 99%

A survey of commonalities relevant to function and dysfunction in pelvic and sexual organs

2007

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Micturition, defecation and sexual function are all programmed through spinal reflexes that are under descending control from higher centres. Interaction between these reflexes can clearly be perceived, and evidence is accumulating the dysfunction in one reflex is often associated with dysfunction in another. In this article, we describe some of the basic properties and neural control of the smooth muscles mediating the reflexes, reviewing the common features that underlie these reflex functions, and what changes may be responsible for dysfunction. We propose that autonomic control within the pelvis predisposes pelvic and sexual organs to crosstalk, with the consequence that diseases and conditions of the pelvis are subject to convergence on a functional level. It should be expected that disturbance of the function of one system will inevitably impact adjacent systems.

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A Quantitative Study of Atropine-Resistant Contractile Responses in Human Detrusor Smooth Muscle, From Stable, Unstable and Obstructed Bladders

Abstract: It is concluded that purinergic, atropine-resistant contractions are present in some types of dysfunctional bladder, and these are not caused by a differential sensitivity of the muscle to ATP and cholinergic agonists.

Cited by 62 publications

References 25 publications

Conscious voiding during bladder obstruction in guinea pigs correlates with contractile activity of isolated bladders

Conscious voiding during bladder obstruction in guinea pigs correlates with contractile activity of isolated bladders

Drug Insight: biological effects of botulinum toxin A in the lower urinary tract

A survey of commonalities relevant to function and dysfunction in pelvic and sexual organs

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