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:10.1016/s0022-5347(05)68247-x

Cited by 211 publications

(131 citation statements)

References 25 publications

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“…Furthermore, since there were no differences in the effects of carbachol or ATP, then the observed increase of the contractile response to EFS must be due to presynaptic mechanisms rather than postsynaptic effects. This would fit with evidence that in neurogenic bladder and hypertrophic unstable bladder syndromes, TTX-sensitive but atropine resistant, purinergic contractions are increased [16, 29–31]. In neurogenic bladder, it was shown that there was a marked increase in the purinergic contribution to parasympathetic control of bladder contractility [15].…”

Section: Discussionsupporting

confidence: 69%

Altered detrusor contractility in MPTP-treated common marmosets with bladder hyperreflexia

et al. 2017

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Bladder hyperreflexia is a common non-motor feature of Parkinson’s disease. We now report on the contractility of the isolated primate detrusor strips devoid of nerve input and show that following MPTP, the amplitude and frequency of spontaneous contraction was increased. These responses were unaffected by dopamine D1 and D2 receptor agonists A77636 and ropinirole respectively. Contractions by exogenous carbachol, histamine or ATP were similar and no differences in the magnitude of noradrenaline-induced relaxation were seen in detrusor strip obtained from normal and MPTP-treated common marmosets (Callithrix jacchus). However, the neurogenic contractions following electrical field stimulation of the intrinsic nerves (EFS) were markedly greater in strips obtained from MPTP treated animals. EFS evoked non-cholinergic contractions following atropine were also greater but the contribution of the cholinergic innervation as a proportion of the overall contraction was smaller in the detrusor strips of MPTP treated animals, suggesting a preferential enhancement of the non-cholinergic transmission. Although dopaminergic mechanism has been proposed to underlie bladder hyperreflexia in MPTP-treated animals with intact bladder, the present data indicates that the increased neurogenically mediated contractions where no extrinsic innervation exists might be due to long-term adaptive changes locally as a result of the loss of the nigrostriatal output.

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Section: Discussionsupporting

confidence: 69%

Altered detrusor contractility in MPTP-treated common marmosets with bladder hyperreflexia

et al. 2017

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“…For example, bladder preparations from interstitial cystitis patients showed increased sensitivity of contractions to purine receptor desensitization with α,β-methylene ATP (Palea et al, 1993). Likewise, bladder detrusor preparations from obstructed bladders demonstrated significant atropine-resistant contractions that were abolished by TTX or by α,β-methylene ATP (Bayliss et al, 1999). P2X1 receptors are believed to be the predominant receptor mediating purinergic contractions in human bladder, and their expression appears to be increased in obstructed bladders compared with control bladders (O’Reilly et al, 2001; O’Reilly et al, 2002).…”

Section: Evidence For Release Of Purine Neurotransmittersmentioning

confidence: 99%

The purinergic neurotransmitter revisited: A single substance or multiple players?

Mutafova‐Yambolieva

Durnin

2014

Pharmacology & Therapeutics

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The past half century has witnessed tremendous advances in our understanding of extracellular purinergic signaling pathways. Purinergic neurotransmission, in particular, has emerged as a key contributor in the efficient control mechanisms in the nervous system. The identity of the purine neurotransmitter, however, remains controversial. Identifying it is difficult because purines are present in all cell types, have a large variety of cell sources, and are released via numerous pathways. Moreover, studies on purinergic neurotransmission have relied heavily on indirect measurements of integrated postjunctional responses that do not provide direct information for neurotransmitter identity. This paper discusses experimental support for adenosine 5′-triphosphate (ATP) as a neurotransmitter and recent evidence for possible contribution of other purines, in addition to or instead of ATP, in chemical neurotransmission in the peripheral, enteric and central nervous systems. Sites of release and action of purines in model systems such as vas deferens, blood vessels, urinary bladder and chromaffin cells are discussed. This is preceded by a brief discussion of studies demonstrating storage of purines in synaptic vesicles. We examine recent evidence for cell type targets (e.g., smooth muscle cells, interstitial cells, neurons and glia) for purine neurotransmitters in different systems. This is followed by brief discussion of mechanisms of terminating the action of purine neurotransmitters, including extracellular nucleotide hydrolysis and possible salvage and reuptake in the cell. The significance of direct neurotransmitter release measurements is highlighted. Possibilities for involvement of multiple purines (e.g., ATP, ADP, NAD+, ADP-ribose, adenosine, and diadenosine polyphosphates) in neurotransmission are considered throughout.

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“…Bladder strips were also used to investigate myogenic and neuronal factors that modulate smooth muscle tone with the aim of discovering ion channels and/or receptors and/or intracellular pathways that could be targeted to induce either relaxation or contraction of the smooth muscle 3,10–13 . Other studies have focused on the nature of neurotransmission, including transmitters and receptors involved and changes induced by pathology 14,15 . In addition, the method has been used for comparisons between tissues from different species 16–18 , between organs 19–21 , and evaluation of drug structure-activity relationships 22–24 .…”

Section: Introductionmentioning

confidence: 99%

Bladder Smooth Muscle Strip Contractility as a Method to Evaluate Lower Urinary Tract Pharmacology

Kullmann

Daugherty

Groat

et al. 2014

JoVE

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We describe an in vitro method to measure bladder smooth muscle contractility, and its use for investigating physiological and pharmacological properties of the smooth muscle as well as changes induced by pathology. This method provides critical information for understanding bladder function while overcoming major methodological difficulties encountered in in vivo experiments, such as surgical and pharmacological manipulations that affect stability and survival of the preparations, the use of human tissue, and/or the use of expensive chemicals. It also provides a way to investigate the properties of each bladder component (i.e. smooth muscle, mucosa, nerves) in healthy and pathological conditions. The urinary bladder is removed from an anesthetized animal, placed in Krebs solution and cut into strips. Strips are placed into a chamber filled with warm Krebs solution. One end is attached to an isometric tension transducer to measure contraction force, the other end is attached to a fixed rod. Tissue is stimulated by directly adding compounds to the bath or by electric field stimulation electrodes that activate nerves, similar to triggering bladder contractions in vivo. We demonstrate the use of this method to evaluate spontaneous smooth muscle contractility during development and after an experimental spinal cord injury, the nature of neurotransmission (transmitters and receptors involved), factors involved in modulation of smooth muscle activity, the role of individual bladder components, and species and organ differences in response to pharmacological agents. Additionally, it could be used for investigating intracellular pathways involved in contraction and/or relaxation of the smooth muscle, drug structure-activity relationships and evaluation of transmitter release. The in vitro smooth muscle contractility method has been used extensively for over 50 years, and has provided data that significantly contributed to our understanding of bladder function as well as to pharmaceutical development of compounds currently used clinically for bladder management.

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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 211 publications

References 25 publications

Altered detrusor contractility in MPTP-treated common marmosets with bladder hyperreflexia

Altered detrusor contractility in MPTP-treated common marmosets with bladder hyperreflexia

The purinergic neurotransmitter revisited: A single substance or multiple players?

Bladder Smooth Muscle Strip Contractility as a Method to Evaluate Lower Urinary Tract Pharmacology

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