Calcium signalling in wound-responsive normal human urothelial cell monolayers

Shabir, Saqib; Southgate, Jennifer

doi:10.1016/j.ceca.2008.02.008

Cited by 49 publications

(61 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Here, we have shown that stimulation of P2 receptors with exogenous ATP enhanced scratch repair, as did the addition of the ecto-ATPase inhibitor ARL-67156, which prevents the breakdown of ATP. In contrast, blockade of P2 activity and Ca 2ϩ signaling inhibited scratch repair in either the presence or absence of ATP (19,26). This indicates that ATP is one of the major factors released upon damage and contributes to the scratch healing phenotype.…”

Section: Discussionmentioning

confidence: 73%

“…For confocal imaging, proliferative urothelial cells derived from the ureter (unless otherwise stated) were grown on 0.1 mg/ml collagen-coated glass coverslips and loaded with 5 M fluo4-AM and 5 M fura red-AM in 0.02% pluronic acid in DMSO for 20 min (19). Coverslips were placed in a perfusion chamber (Warner Instruments) with a constant flow rate of 1.5 ml/min and positioned on a Revolution XD spinning disc confocal microscope (Andor) with a scan rate of 1 image/s.…”

Section: Methodsmentioning

confidence: 99%

“…30). There has been limited characterization of these receptor/mediator signaling pathways in the human urothelium, where functional TRPV1 (10) and an autocrine-activated P2Y receptor pathway (19,26) have been reported. Ultimately, this conflict and the lack of consensus are hindrances to the development of selective drugs.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Functional expression of purinergic P2 receptors and transient receptor potential channels by the human urothelium

Shabir

Cross

Kirkwood

et al. 2013

American Journal of Physiology-Renal Physiology

Self Cite

View full text Add to dashboard Cite

In addition to its role as a physical barrier, the urothelium is considered to play an active role in mechanosensation. A key mechanism is the release of transient mediators that activate purinergic P2 receptors and transient receptor potential (TRP) channels to effect changes in intracellular Ca²⁺. Despite the implied importance of these receptors and channels in urothelial tissue homeostasis and dysfunctional bladder disease, little is known about their functional expression by the human urothelium. To evaluate the expression and function of P2X and P2Y receptors and TRP channels, the human ureter and bladder were used to separate urothelial and stromal tissues for RNA isolation and cell culture. RT-PCR using stringently designed primer sets was used to establish which P2 and TRP species were expressed at the transcript level, and selective agonists/antagonists were used to confirm functional expression by monitoring changes in intracellular Ca²⁺ and in a scratch repair assay. The results confirmed the functional expression of P2Y₄ receptors and excluded nonexpressed receptors/channels (P2X₁, P2X₃, P2X₆, P2Y₆, P2Y₁₁, TRPV5, and TRPM8), while a dearth of specific agonists confounded the functional validation of expressed P2X₂, P2X₄, P2Y₁, P2Y₂, TRPV2, TRPV3, TRPV6 and TRPM7 receptors/channels. Although a conventional response was elicited in control stromal-derived cells, the urothelial cell response to well-characterized TRPV1 and TRPV4 agonists/antagonists revealed unexpected anomalies. In addition, agonists that invoked an increase in intracellular Ca²⁺ promoted urothelial scratch repair, presumably through the release of ATP. The study raises important questions about the ligand selectivity of receptor/channel targets expressed by the urothelium. These pathways are important in urothelial tissue homeostasis, and this opens the possibility of selective drug targeting.

show abstract

Section: Discussionmentioning

confidence: 73%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Functional expression of purinergic P2 receptors and transient receptor potential channels by the human urothelium

Shabir

Cross

Kirkwood

et al. 2013

American Journal of Physiology-Renal Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Under resting conditions, cytoplasmic calcium concentration is maintained at approximately 100nM [30]. When stimulated, calcium enters the cell from extracellular stores via ion channels in the plasma membrane or it is released from intracellular stores through channels and receptors in the endoplasmic reticulum [30]. These channels may be activated and modulated by second messengers including IP 3 , which is produced by binding of ligands, such as ATP, to GPCRs [31].…”

Section: Cannabinoid Receptor Signalingmentioning

confidence: 99%

“…Calcium acts as an intracellular messenger where it plays a key role in regulating basic cellular responses, such as migration and proliferation [30]. Under resting conditions, cytoplasmic calcium concentration is maintained at approximately 100nM [30].…”

Section: Cannabinoid Receptor Signalingmentioning

confidence: 99%

Cannabinoids and the Urinary Bladder

Bakali¹

2013

Gynecol Obstet

View full text Add to dashboard Cite

The presence of the Endocannabinoid System (ECS) in the urinary bladder has led to speculation that endocannabinoid-signalling is involved in the signal transduction pathways regulating bladder relaxation and may be involved in pathophysiological processes of the bladder. On the basis of this evidence, it was postulated that the binding of endocannabinoids to the cannabinoid receptors (CB 1 and CB 2 ) may result in relaxation of the urinary bladder during the filling phase. Dysregulation of the ECS in human bladder may be responsible for the aetiopathogenesis of Overactive Bladder Syndrome (OAB) and Detrusor Overactivity (DO).

show abstract

Calcium‐dependent antimicrobials: Nature‐inspired materials and designs

Wang,

Zeng,

Ahmed

et al. 2024

Exploration

View full text Add to dashboard Cite

Bacterial infection remains a major complication answering for the failures of various implantable medical devices. Tremendous extraordinary advances have been published in the design and synthesis of antimicrobial materials addressing this issue; however, the clinical translation has largely been blocked due to the challenge of balancing the efficacy and safety of these materials. Here, calcium's biochemical features, natural roles in pathogens and the immune systems, and advanced uses in infection medications are illuminated, showing calcium is a promising target for developing implantable devices with less infection tendency. The paper gives a historical overview of biomedical uses of calcium and summarizes calcium's merits in coordination, hydration, ionization, and stereochemistry for acting as a structural former or trigger in biological systems. It focuses on the involvement of calcium in pathogens’ integrity, motility, and metabolism maintenance, outlining the potential antimicrobial targets for calcium. It addresses calcium's uses in the immune systems that the authors can learn from for antimicrobial synthesis. Additionally, the advances in calcium's uses in infection medications are highlighted to sketch the future directions for developing implantable antimicrobial materials. In conclusion, calcium is at the nexus of antimicrobial defense, and future works on taking advantage of calcium in antimicrobial developments are promising in clinical translation.

show abstract

Calcium signalling in wound-responsive normal human urothelial cell monolayers

Cited by 49 publications

References 25 publications

Functional expression of purinergic P2 receptors and transient receptor potential channels by the human urothelium

Functional expression of purinergic P2 receptors and transient receptor potential channels by the human urothelium

Cannabinoids and the Urinary Bladder

Calcium‐dependent antimicrobials: Nature‐inspired materials and designs

Contact Info

Product

Resources

About