Evidence map›Paper›PMID 24167028›Full record

ArticleNeurourology and urodynamics2015

Effect of botulinum toxin A on urothelial-release of ATP and expression of SNARE targets within the urothelium.

Ann T Hanna-Mitchell, Amanda S Wolf-Johnston, Stacey R Barrick, Anthony J Kanai, Michael B Chancellor, William C de Groat, Lori A Birder

Open access · greenAbstract read
In one paragraph

Article in Neurourology and urodynamics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 2 pooled it
6.2field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 2 syntheses or guidelines pooled it, 67 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Ann T Hanna-MitchellDepartment of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Amanda S Wolf-Johnston
Stacey R Barrick
Anthony J Kanai
Michael B Chancellor
William C de Groat
Lori A Birder
University of Pittsburgh · USOakland University · US

Funding

Urothelium in Detrusor OveractivityP01DK093424 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DEGROAT, WILLIAM C · 2013 to 2017
$7.9M
PDE5 Inhibition of Afferents and Interstitial Cells in Overactive Mouse BladdersR01DK098361 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BIRDER, LORI A, KANAI, ANTHONY JOHN · 2014 to 2024
$5.7M
ROLE OF NITRIC OXIDE IN INTERSTITIAL CYSTITISR01DK057284 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BIRDER, LORI A · 2000 to 2014
$4.3M
Roles of Nitric Oxide and Superoxide in CystitisR01DK071085 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KANAI, ANTHONY JOHN · 2005 to 2017
$3.3M
Nitric Oxide in Bladder Neural-Epithelial SignalingR37DK054824 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BIRDER, LORI A · 2007 to 2016
$3.0M
Evaluation of Stimulus-Evoked Membrane Trafficking in Bladder Urothelial CellsK01DK080184 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI HANNA-MITCHELL, ANN THERESA · 2009 to 2013
$604k
Intravesical liposome drug delivery to treat interstitial cystitisR01DK083323 · NIDDK · WILLIAM BEAUMONT HOSPITAL RESEARCH INST · PI CHANCELLOR, MICHAEL B · 2010 to 2012
$603k
NIDDK NIH HHS K01 DK080184NIDDK NIH HHS P01 DK093424NIDDK NIH HHS R01 DK057284NIDDK NIH HHS R01 DK071085NIDDK NIH HHS R01 DK083323NIDDK NIH HHS R01 DK098361NIDDK NIH HHS R01 DK57284NIDDK NIH HHS R37 DK054824NIDDK NIH HHS R37 DK54824
6 · The paper itself

Abstract

aimsBotulinum neurotoxin serotype A (BoNT/A) has emerged as an effective treatment of urinary bladder overactivity. Intravesical lipotoxin (BoNT/A delivery using liposomes), which may target the urothelium, is effective in blocking acetic acid induced hyperactivity in animals. The objective of this study was to assess the possible site of toxin action within the urothelium.

methodsWe examined expression of the toxin receptor (SV2) and its cleavage targets (SNAP-25 and SNAP-23) within urothelium as well as effects of the toxin on mechanically evoked release of ATP from cultured rat urothelial cells. ATP release was measured using the luciferin-luciferase assay; we examined expression of SNAP-23 and -25 in urothelial cells and mucosa of rat and human bladders.

resultsBoNT/A (1.5 U; 1-3 hr) blocked hypotonic evoked release of urothelial ATP, without affecting morphology. The expression of protein targets for BoNT/A binding (SV2) was detected in human and rat bladder mucosa and catalytic action (SNAP-23, -25) in urothelial cells and mucosa (differed in intensity) from rat and human bladder. Incubation of cultured (rat) urothelial cells with BoNT/A decreased expression levels of both SNAP-23 (44%) and SNAP-25 (80%).

conclusionsOur findings reveal that the bladder urothelium expresses the intracellular targets and the binding protein for cellular uptake of BoNT/A; and that the toxin is able to suppress the levels of these targets as well as hypotonic-evoked ATP release. These data raise the possibility that intravesical treatment with BoNT/A suppresses bladder reflex and sensory mechanisms by affecting a number of urothelial functions including release of transmitters.

Indexed as

Acetylcholine Release InhibitorsAdenosine TriphosphateAnimalsBotulinum Toxins, Type ACells, CulturedHumansMembrane GlycoproteinsMuscle ContractionMuscle, SmoothNerve Tissue ProteinsRatsSynaptosomal-Associated Protein 25Urinary BladderUrinary Bladder, OveractiveUrotheliumVesicular Transport ProteinsAcetylcholine Release InhibitorsAdenosine TriphosphateBotulinum Toxins, Type AMembrane GlycoproteinsNerve Tissue ProteinsSnap23 protein, ratSnap25 protein, ratSv2a protein, ratSynaptosomal-Associated Protein 25Vesicular Transport Proteinsbladder mucosaexocytosisSNAP-23SNAP-25

Identifiers

PMID24167028
PMCPMC4035459
OpenAlexW1763431178

What OpenQuestion holds

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Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.