ArticleJCI insight2019
Targetable purinergic receptors P2Y12 and A2b antagonistically regulate bladder function.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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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.
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.
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Who cites it
20 citing papers in PubMed, 34 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
- Adenosine and acute low oxygen conditions suppress urinary bladder contractility through the activation of adenosine 2B receptors and large-conductance calcium-activated potassium channels.The Journal of physiology · 2026Article
- ML-UrineQuant: A machine learning program for identifying and quantifying mouse urine on absorbent paper.Physiological reports · 2025Article
- Adiponectin signaling regulates urinary bladder function by blunting smooth muscle purinergic contractility.JCI insight · 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
- Ectonucleotidases and purinergic receptors in mouse prostate gland.American journal of clinical and experimental urology · 2025Article
- Role of ecto-5'-nucleotidase in bladder function activity and smooth muscle contractility.Purinergic signalling · 2024Article
- Advancing Pain Understanding and Drug Discovery: Insights from Preclinical Models and Recent Research Findings.Pharmaceuticals (Basel, Switzerland) · 2024Review
- DREADD agonist compound 21 causes acute diuresis in wild-type mice.Frontiers in pharmacology · 2024Article
- Spatial mapping of ectonucleotidase gene expression in the murine urinary bladder.Frontiers in physiology · 2023Article
- Smooth Muscle Insulin Receptor Deletion Causes Voiding Dysfunction: A Mechanism for Diabetic Bladder Dysfunction.Diabetes · 2022Article
- Combination and Novel Pharmacologic Agents for OAB.Current urology reports · 2022Review
- Deletion of Mechanosensory β1-integrin From Bladder Smooth Muscle Results in Voiding Dysfunction and Tissue Remodeling.Function (Oxford, England) · 2022Article
- Reviving Cav1.2 as an attractive drug target to treat bladder dysfunction.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Review
- 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
- NMDAR in bladder smooth muscle is not a pharmacotherapy target for overactive bladder in mice.PeerJ · 2021Article
- The Urothelium: Life in a Liquid Environment.Physiological reviews · 2020Review
- Disruption of Cav1.2-mediated signaling is a pathway for ketamine-induced pathology.Nature communications · 2020Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
Abnormalities in purine availability or purinergic receptor density are commonly seen in patients with lower urinary tract symptoms (LUTS), but the underlying mechanisms relating altered receptor function to LUTS are unknown. Here we provide extensive evidence for the reciprocal interplay of multiple receptors responding to ATP, ADP (adenosine diphosphate), and adenosine, agonists that regulate bladder function significantly. ADP stimulated P2Y12 receptors, causing bladder smooth muscle (BSM) contraction, whereas adenosine signaling through potentially newly defined A2b receptors, actively inhibited BSM purinergic contractility. The modulation of adenylyl cyclase-cAMP signaling via A2b and P2Y12 interaction actively regulated bladder contractility by modulating intracellular calcium levels. KO mice lacking the receptors display diametrically opposed bladder phenotypes, with P2Y12-KO mice exhibiting an underactive bladder (UAB) phenotype with increased bladder capacity and reduced voiding frequency, whereas A2b-KO mice have an overactive bladder (OAB), with decreased capacity and increased voiding frequency. The opposing phenotypes in P2Y12-KO and A2b-KO mice not only resulted from dysregulated BSM contractility, but also from abnormal BSM cell growth. Finally, we demonstrate that i.p. administration of drugs targeting P2Y12 or A2b receptor rescues these abnormal phenotypes in both KO mice. These findings strongly indicate that P2Y12 and A2b receptors are attractive therapeutic targets for human patients with LUTS.
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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.