ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2014
ADP-induced bladder contractility is mediated by P2Y12 receptor and temporally regulated by ectonucleotidases and adenosine signaling.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Biomechanical regulation of bladder injury and repair.Nature reviews. Urology · 2026Review
- Dysregulation of CD39/Ectonucleoside Triphosphate Diphosphohydrolase 1 Causes Urinary Bladder Dysfunction with Abnormal Smooth Muscle Contractility.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Adiponectin signaling regulates urinary bladder function by blunting smooth muscle purinergic contractility.JCI insight · 2025Article
- Ectonucleotidases and purinergic receptors in mouse prostate gland.American journal of clinical and experimental urology · 2025Article
- Editorial: Novel mechanisms involved in urinary bladder control: advances in neural, humoral and local factors underlying function and disease, volume III.Frontiers in physiology · 2025Article
- Role of ecto-5'-nucleotidase in bladder function activity and smooth muscle contractility.Purinergic signalling · 2024Article
- Impact of Vitamin D deficiency on immunological and metabolic responses in women with recurrent pregnancy loss: focus on VDBP/HLA-G1/CTLA-4/ENTPD1/adenosine-fetal-maternal conflict crosstalk.BMC pregnancy and childbirth · 2024Article
- Spatial mapping of ectonucleotidase gene expression in the murine urinary bladder.Frontiers in physiology · 2023Article
- P2 purinergic receptor dysregulation in urologic disease.Purinergic signalling · 2022Review
- Mechanosensitive Hydrolysis of ATP and ADP in Lamina Propria of the Murine Bladder by Membrane-Bound and Soluble Nucleotidases.Frontiers in physiology · 2022Article
- Molecular mechanisms of voiding dysfunction in a novel mouse model of acute urinary retention.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- NTPDase1 Modulates Smooth Muscle Contraction in Mice Bladder by Regulating Nucleotide Receptor Activation Distinctly in Male and Female.Biomolecules · 2021Article
- Disruption of Cav1.2-mediated signaling is a pathway for ketamine-induced pathology.Nature communications · 2020Article
- Targetable purinergic receptors P2Y12 and A2b antagonistically regulate bladder function.JCI insight · 2019Article
- An ex vivo bladder model with detrusor smooth muscle removed to analyse biologically active mediators released from the suburothelium.The Journal of physiology · 2019Article
- Proteomic Analysis of Urothelium of Rats with Detrusor Overactivity Induced by Bladder Outlet Obstruction.Molecular & cellular proteomics : MCP · 2018Article
- Urothelial purine release during filling of murine and primate bladders.American journal of physiology. Renal physiology · 2016Article
- Reduced Expression of P2Y2 Receptor and Acetylcholinesterase at Neuromuscular Junction of P2Y1 Receptor Knock-out Mice.Journal of molecular neuroscience : MN · 2015Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Purinergic signaling comprises one key pathway in modulating bladder smooth muscle (BSM) contractility, disorders of which become highly prevalent with aging. ADP was first observed to modulate BSM contractility >40 yr ago, yet the underlying molecular mechanism still remains unclear. Here, we demonstrate, using myography, that ADP and ADPβS dose-dependently induce mouse BSM contraction, and ADP-induced BSM contraction is blocked by a selective P2Y12 receptor (P2Y12R) antagonist, PSB 0739 (25 μM), but is unaffected by P2Y1 and P2Y13 receptor antagonists. P2Y12R in BSM exhibits distinct pharmacological properties that are different from P2Y12R in platelets. After an immediate contraction, prolonged exposure to ADP causes BSM to become refractory to further ADP-mediated contraction. However, in mice lacking ectonucleotidases Entpd1 (ATP→ADP→AMP) or Nt5e (AMP→adenosine), or by inhibiting adenosine signaling, the refractory response was altered, resulting in repeated BSM contractions in response to repeated ADP (0.1-1 mM) stimulation. Our data indicate that P2Y12R undergoes slow desensitization; ADP-P2Y12 signaling is tightly regulated by Entpd1/Nt5e activity and adenosine receptors; and ADP-adenosine signaling play an important role in modulating P2X-mediated BSM contraction. The identification of P2Y12R in BSM, and the current clinical availability of P2Y12R inhibitors, such as clopidogrel, offers potentially novel treatment strategies for bladder contractility disorders.
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Registered trials
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.