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Bradykinin modulates spontaneous nerve growth factor production and stretch-induced ATP release in human urothelium

Overview of attention for article published in Pharmacological Research, February 2013
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Title
Bradykinin modulates spontaneous nerve growth factor production and stretch-induced ATP release in human urothelium
Published in
Pharmacological Research, February 2013
DOI 10.1016/j.phrs.2013.01.010
Pubmed ID
Authors

Peter Ochodnický, Martina B. Michel, Jan J. Butter, Jai Seth, Jalesh N. Panicker, Martin C. Michel

Abstract

The urothelium plays a crucial role in integrating urinary bladder sensory outputs, responding to mechanical stress and chemical stimulation by producing several diffusible mediators, including ATP and, possibly, neurotrophin nerve growth factor (NGF). Such urothelial mediators activate underlying afferents and thus may contribute to normal bladder sensation and possibly to the development of bladder overactivity. The muscle-contracting and pain-inducing peptide bradykinin is produced in various inflammatory and non-inflammatory pathologies associated with bladder overactivity, but the effect of bradykinin on human urothelial function has not yet been characterized. The human urothelial cell line UROtsa expresses mRNA for both B1 and B2 subtypes of bradykinin receptors, as determined by real-time PCR. Bradykinin concentration-dependently (pEC50=8.3, Emax 4434±277nM) increased urothelial intracellular calcium levels and induced phosphorylation of the mitogen-activated protein kinase (MAPK) ERK1/2. Activation of both bradykinin-induced signaling pathways was completely abolished by the B2 antagonist icatibant (1μM), but not the B1 antagonist R715 (1μM). Bradykinin-induced (100nM) B2 receptor activation markedly increased (192±13% of control levels) stretch-induced ATP release from UROtsa in hypotonic medium, the effect being dependent on intracellular calcium elevations. UROtsa cells also expressed mRNA and protein for NGF and spontaneously released NGF to the medium in the course of hours (11.5±1.4pgNGF/mgprotein/h). Bradykinin increased NGF mRNA expression and accelerated urothelial NGF release to 127±5% in a protein kinase C- and ERK1/2-dependent manner. Finally, bradykinin up-regulated mRNA for transient-receptor potential vanilloid (TRPV1) sensory ion channel in UROtsa. In conclusion, we show that bradykinin represents a versatile modulator of human urothelial phenotype, accelerating stretch-induced ATP release, spontaneous release of NGF, as well as expression of sensory ion channel TRPV1. Bradykinin-induced changes in urothelial sensory function might contribute to the development of bladder dysfunction.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 27 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 4%
Unknown 26 96%

Demographic breakdown

Readers by professional status Count As %
Researcher 5 19%
Student > Bachelor 5 19%
Student > Ph. D. Student 5 19%
Student > Master 4 15%
Student > Doctoral Student 2 7%
Other 5 19%
Unknown 1 4%
Readers by discipline Count As %
Medicine and Dentistry 10 37%
Agricultural and Biological Sciences 5 19%
Business, Management and Accounting 2 7%
Neuroscience 2 7%
Immunology and Microbiology 1 4%
Other 2 7%
Unknown 5 19%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 01 March 2013.
All research outputs
#17,285,668
of 25,373,627 outputs
Outputs from Pharmacological Research
#2,289
of 3,503 outputs
Outputs of similar age
#193,953
of 291,217 outputs
Outputs of similar age from Pharmacological Research
#5
of 7 outputs
Altmetric has tracked 25,373,627 research outputs across all sources so far. This one is in the 21st percentile – i.e., 21% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,503 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.9. This one is in the 28th percentile – i.e., 28% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 291,217 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 24th percentile – i.e., 24% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 7 others from the same source and published within six weeks on either side of this one. This one has scored higher than 2 of them.