ArticleJournal of the American Society of Nephrology : JASN2015
P2Y12 Receptor Localizes in the Renal Collecting Duct and Its Blockade Augments Arginine Vasopressin Action and Alleviates Nephrogenic Diabetes Insipidus.
Article in Journal of the American Society of Nephrology : JASN, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 52 citations in OpenAlex.
- Pharmacological interaction and immune response of purinergic receptors in therapeutic modulation.Purinergic signalling · 2024Review
- Refractory drug-induced systemic small-vessel vasculitis with two varied extracutaneous manifestations: a case report and review of the literature.Journal of medical case reports · 2023Review
- Circulating and Urinary Concentrations of Malondialdehyde in Aging Humans in Health and Disease: Review and Discussion.Biomedicines · 2023Review
- Diagnostic and therapeutic value of P2Y12R in epilepsy.Frontiers in pharmacology · 2023Review
- Type 2 Diabetes Mellitus (T2DM) and Carbohydrate Metabolism in Relation to T2DM from Endocrinology, Neurophysiology, Molecular Biology, and Biochemistry Perspectives.Evidence-based complementary and alternative medicine : eCAM · 2022Review
- Tenascin-C fibronectin D domain is involved in the fine-tuning of glial response to CNS injuryFrontiers in cell and developmental biology · 2022Article
- Updates and Perspectives on Aquaporin-2 and Water Balance Disorders.International journal of molecular sciences · 2021Review
- An AMPK activator as a therapeutic option for congenital nephrogenic diabetes insipidus.JCI insight · 2021Article
- The Role of Vasopressin V2 Receptor in Drug-Induced Hyponatremia.Frontiers in physiology · 2021Review
- Conversion of extracellular ATP into adenosine: a master switch in renal health and disease.Nature reviews. Nephrology · 2020Review
- Article
- Targeting the Trafficking of Kidney Water Channels for Therapeutic Benefit.Annual review of pharmacology and toxicology · 2020Review
- Extracellular Nucleotides and P2 Receptors in Renal Function.Physiological reviews · 2020Review
- P2YFrontiers in endocrinology · 2020Article
- Osmoregulation Performance and Kidney Transplant Outcome.Journal of the American Society of Nephrology : JASN · 2019Article
- Mammalian urine concentration: a review of renal medullary architecture and membrane transporters.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2018Review
- Genetic Deletion of P2YFrontiers in physiology · 2018Article
- Acute In Vivo Analysis of ATP Release in Rat Kidneys in Response to Changes of Renal Perfusion Pressure.Journal of the American Heart Association · 2017Article
- Prasugrel suppresses development of lithium-induced nephrogenic diabetes insipidus in mice.Purinergic signalling · 2017Article
- Role of adenylyl cyclase 6 in the development of lithium-induced nephrogenic diabetes insipidus.JCI insight · 2017Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
P2Y12 receptor (P2Y12-R) signaling is mediated through Gi, ultimately reducing cellular cAMP levels. Because cAMP is a central modulator of arginine vasopressin (AVP)-induced water transport in the renal collecting duct (CD), we hypothesized that if expressed in the CD, P2Y12-R may play a role in renal handling of water in health and in nephrogenic diabetes insipidus. We found P2Y12-R mRNA expression in rat kidney, and immunolocalized its protein and aquaporin-2 (AQP2) in CD principal cells. Administration of clopidogrel bisulfate, an irreversible inhibitor of P2Y12-R, significantly increased urine concentration and AQP2 protein in the kidneys of Sprague-Dawley rats. Notably, clopidogrel did not alter urine concentration in Brattleboro rats that lack AVP. Clopidogrel administration also significantly ameliorated lithium-induced polyuria, improved urine concentrating ability and AQP2 protein abundance, and reversed the lithium-induced increase in free-water excretion, without decreasing blood or kidney tissue lithium levels. Clopidogrel administration also augmented the lithium-induced increase in urinary AVP excretion and suppressed the lithium-induced increase in urinary nitrates/nitrites (nitric oxide production) and 8-isoprostane (oxidative stress). Furthermore, selective blockade of P2Y12-R by the reversible antagonist PSB-0739 in primary cultures of rat inner medullary CD cells potentiated the expression of AQP2 and AQP3 mRNA, and cAMP production induced by dDAVP (desmopressin). In conclusion, pharmacologic blockade of renal P2Y12-R increases urinary concentrating ability by augmenting the effect of AVP on the kidney and ameliorates lithium-induced NDI by potentiating the action of AVP on the CD. This strategy may offer a novel and effective therapy for lithium-induced NDI.
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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.