ArticleCirculation research2018
Pannexin 1 Channels as an Unexpected New Target of the Anti-Hypertensive Drug Spironolactone.
Open access · bronzeAbstract read
In one paragraph
Article in Circulation research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed
3.6field-weighted citation impact, top 6% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
71 citing papers in PubMed, 107 citations in OpenAlex.
- Old drug with new application: spironolactone suppresses Panx 1-mediated CaInflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Pannexin 1 phosphorylation sites differentially modulate channel activity and physiological outcomes.bioRxiv : the preprint server for biology · 2026Article
- Tubular epithelial cells promote macrophage pyroptosis through PANX1-extracellular ATP-P2X7 signaling in aldosterone-dependent renal injury.Cell death & disease · 2026Article
- Dissecting the role of mineralocorticoid receptors in binge-like alcohol drinking in mice: Finerenone as a potential pharmacotherapy.Psychopharmacology · 2026Article
- Pannexins in the heart: cell-specific expression and contributions to disease.Cell and tissue research · 2026Review
- Connexin-Pannexin duality in glioblastoma.Cell and tissue research · 2026Review
- Panx1 and drug discovery: from non-specific inhibitors to tailored drug compounds.Cell and tissue research · 2026Review
- Pannexins in the vasculature.American journal of physiology. Heart and circulatory physiology · 2025Review
- Impact of Endothelial Diversity and Dysfunction on Cardiovascular Disease.Comprehensive Physiology · 2025Review
- Pannexin channels in the kidney.American journal of physiology. Renal physiology · 2025Review
- Innate detection ofbioRxiv : the preprint server for biology · 2025Article
- Arterial Myocyte Pannexin 1 Channel Controls Vascular Reactivity in Diabetic Hyperglycemia.Circulation research · 2025Article
- Pannexin 1 and pannexin 3 differentially regulate the cancer cell properties of cutaneous squamous cell carcinoma.The Journal of physiology · 2025Article
- Pannexin 1 crosstalk with the Hippo pathway in malignant melanoma.The FEBS journal · 2025Article
- Novel Naphthyridones Targeting Pannexin 1 for Colitis Management.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Distinct properties and activation of hexameric and heptameric Pannexin 1 channel concatemers.The Journal of general physiology · 2025Article
- Pannexin channels in inflammation and tumorigenesis.Frontiers in cell and developmental biology · 2025Review
- Dual Regulatory Roles of Pannexin 1 in the Pathogenesis and Recovery of Sepsis-Induced Acute Lung Injury.Infection and drug resistance · 2025Review
- Molecular and metabolic landscape of adenosine triphosphate-induced cell death in cardiovascular disease.World journal of cardiology · 2024Review
- Finerenone attenuates downregulation of the kidney GLP-1 receptor and glucagon receptor and cardiac GIP receptor in mice with comorbid diabetes.Diabetology & metabolic syndrome · 2024Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
- Commented on by
Authors and funding
16 authors at 3 institutions in 2 countries.
Miranda E GoodFrom the Department of Molecular Physiology and Biophysics, Robert M. Berne Cardiovascular Research Center (M.E.G., J.T.B., L.J.D., A.W.L., B.E.I.), Department of Pharmacology (Y.-H.C., S.K.M., N.L., B.N.D., D.A.B.), Department of Microbiology, Immunology and Cancer Biology, the Center for Cell Clearance, and the Beirne B. Carter Center for Immunology Research (C.B.M., U.M.L., K.S.R.), and Division of Endocrinology (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Biochemistry and Genetics, La Trobe University, Melbourne, Australia (I.K.H.P.); and Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA (I.Z.J.).
Yu-Hsin ChiuFrom the Department of Molecular Physiology and Biophysics, Robert M. Berne Cardiovascular Research Center (M.E.G., J.T.B., L.J.D., A.W.L., B.E.I.), Department of Pharmacology (Y.-H.C., S.K.M., N.L., B.N.D., D.A.B.), Department of Microbiology, Immunology and Cancer Biology, the Center for Cell Clearance, and the Beirne B. Carter Center for Immunology Research (C.B.M., U.M.L., K.S.R.), and Division of Endocrinology (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Biochemistry and Genetics, La Trobe University, Melbourne, Australia (I.K.H.P.); and Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA (I.Z.J.).
Ivan K H PoonFrom the Department of Molecular Physiology and Biophysics, Robert M. Berne Cardiovascular Research Center (M.E.G., J.T.B., L.J.D., A.W.L., B.E.I.), Department of Pharmacology (Y.-H.C., S.K.M., N.L., B.N.D., D.A.B.), Department of Microbiology, Immunology and Cancer Biology, the Center for Cell Clearance, and the Beirne B. Carter Center for Immunology Research (C.B.M., U.M.L., K.S.R.), and Division of Endocrinology (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Biochemistry and Genetics, La Trobe University, Melbourne, Australia (I.K.H.P.); and Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA (I.Z.J.).
Christopher B MedinaFrom the Department of Molecular Physiology and Biophysics, Robert M. Berne Cardiovascular Research Center (M.E.G., J.T.B., L.J.D., A.W.L., B.E.I.), Department of Pharmacology (Y.-H.C., S.K.M., N.L., B.N.D., D.A.B.), Department of Microbiology, Immunology and Cancer Biology, the Center for Cell Clearance, and the Beirne B. Carter Center for Immunology Research (C.B.M., U.M.L., K.S.R.), and Division of Endocrinology (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Biochemistry and Genetics, La Trobe University, Melbourne, Australia (I.K.H.P.); and Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA (I.Z.J.).
Joshua T ButcherFrom the Department of Molecular Physiology and Biophysics, Robert M. Berne Cardiovascular Research Center (M.E.G., J.T.B., L.J.D., A.W.L., B.E.I.), Department of Pharmacology (Y.-H.C., S.K.M., N.L., B.N.D., D.A.B.), Department of Microbiology, Immunology and Cancer Biology, the Center for Cell Clearance, and the Beirne B. Carter Center for Immunology Research (C.B.M., U.M.L., K.S.R.), and Division of Endocrinology (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Biochemistry and Genetics, La Trobe University, Melbourne, Australia (I.K.H.P.); and Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA (I.Z.J.).
Suresh K MenduFrom the Department of Molecular Physiology and Biophysics, Robert M. Berne Cardiovascular Research Center (M.E.G., J.T.B., L.J.D., A.W.L., B.E.I.), Department of Pharmacology (Y.-H.C., S.K.M., N.L., B.N.D., D.A.B.), Department of Microbiology, Immunology and Cancer Biology, the Center for Cell Clearance, and the Beirne B. Carter Center for Immunology Research (C.B.M., U.M.L., K.S.R.), and Division of Endocrinology (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Biochemistry and Genetics, La Trobe University, Melbourne, Australia (I.K.H.P.); and Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA (I.Z.J.).
Leon J DeLalioFrom the Department of Molecular Physiology and Biophysics, Robert M. Berne Cardiovascular Research Center (M.E.G., J.T.B., L.J.D., A.W.L., B.E.I.), Department of Pharmacology (Y.-H.C., S.K.M., N.L., B.N.D., D.A.B.), Department of Microbiology, Immunology and Cancer Biology, the Center for Cell Clearance, and the Beirne B. Carter Center for Immunology Research (C.B.M., U.M.L., K.S.R.), and Division of Endocrinology (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Biochemistry and Genetics, La Trobe University, Melbourne, Australia (I.K.H.P.); and Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA (I.Z.J.).
Alexander W LohmanFrom the Department of Molecular Physiology and Biophysics, Robert M. Berne Cardiovascular Research Center (M.E.G., J.T.B., L.J.D., A.W.L., B.E.I.), Department of Pharmacology (Y.-H.C., S.K.M., N.L., B.N.D., D.A.B.), Department of Microbiology, Immunology and Cancer Biology, the Center for Cell Clearance, and the Beirne B. Carter Center for Immunology Research (C.B.M., U.M.L., K.S.R.), and Division of Endocrinology (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Biochemistry and Genetics, La Trobe University, Melbourne, Australia (I.K.H.P.); and Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA (I.Z.J.).
Norbert LeitingerFrom the Department of Molecular Physiology and Biophysics, Robert M. Berne Cardiovascular Research Center (M.E.G., J.T.B., L.J.D., A.W.L., B.E.I.), Department of Pharmacology (Y.-H.C., S.K.M., N.L., B.N.D., D.A.B.), Department of Microbiology, Immunology and Cancer Biology, the Center for Cell Clearance, and the Beirne B. Carter Center for Immunology Research (C.B.M., U.M.L., K.S.R.), and Division of Endocrinology (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Biochemistry and Genetics, La Trobe University, Melbourne, Australia (I.K.H.P.); and Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA (I.Z.J.).
Eugene BarrettFrom the Department of Molecular Physiology and Biophysics, Robert M. Berne Cardiovascular Research Center (M.E.G., J.T.B., L.J.D., A.W.L., B.E.I.), Department of Pharmacology (Y.-H.C., S.K.M., N.L., B.N.D., D.A.B.), Department of Microbiology, Immunology and Cancer Biology, the Center for Cell Clearance, and the Beirne B. Carter Center for Immunology Research (C.B.M., U.M.L., K.S.R.), and Division of Endocrinology (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Biochemistry and Genetics, La Trobe University, Melbourne, Australia (I.K.H.P.); and Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA (I.Z.J.).
Ulrike M LorenzFrom the Department of Molecular Physiology and Biophysics, Robert M. Berne Cardiovascular Research Center (M.E.G., J.T.B., L.J.D., A.W.L., B.E.I.), Department of Pharmacology (Y.-H.C., S.K.M., N.L., B.N.D., D.A.B.), Department of Microbiology, Immunology and Cancer Biology, the Center for Cell Clearance, and the Beirne B. Carter Center for Immunology Research (C.B.M., U.M.L., K.S.R.), and Division of Endocrinology (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Biochemistry and Genetics, La Trobe University, Melbourne, Australia (I.K.H.P.); and Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA (I.Z.J.).
Bimal N DesaiFrom the Department of Molecular Physiology and Biophysics, Robert M. Berne Cardiovascular Research Center (M.E.G., J.T.B., L.J.D., A.W.L., B.E.I.), Department of Pharmacology (Y.-H.C., S.K.M., N.L., B.N.D., D.A.B.), Department of Microbiology, Immunology and Cancer Biology, the Center for Cell Clearance, and the Beirne B. Carter Center for Immunology Research (C.B.M., U.M.L., K.S.R.), and Division of Endocrinology (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Biochemistry and Genetics, La Trobe University, Melbourne, Australia (I.K.H.P.); and Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA (I.Z.J.).
Iris Z JaffeFrom the Department of Molecular Physiology and Biophysics, Robert M. Berne Cardiovascular Research Center (M.E.G., J.T.B., L.J.D., A.W.L., B.E.I.), Department of Pharmacology (Y.-H.C., S.K.M., N.L., B.N.D., D.A.B.), Department of Microbiology, Immunology and Cancer Biology, the Center for Cell Clearance, and the Beirne B. Carter Center for Immunology Research (C.B.M., U.M.L., K.S.R.), and Division of Endocrinology (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Biochemistry and Genetics, La Trobe University, Melbourne, Australia (I.K.H.P.); and Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA (I.Z.J.).
Douglas A BaylissFrom the Department of Molecular Physiology and Biophysics, Robert M. Berne Cardiovascular Research Center (M.E.G., J.T.B., L.J.D., A.W.L., B.E.I.), Department of Pharmacology (Y.-H.C., S.K.M., N.L., B.N.D., D.A.B.), Department of Microbiology, Immunology and Cancer Biology, the Center for Cell Clearance, and the Beirne B. Carter Center for Immunology Research (C.B.M., U.M.L., K.S.R.), and Division of Endocrinology (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Biochemistry and Genetics, La Trobe University, Melbourne, Australia (I.K.H.P.); and Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA (I.Z.J.).
Brant E IsaksonFrom the Department of Molecular Physiology and Biophysics, Robert M. Berne Cardiovascular Research Center (M.E.G., J.T.B., L.J.D., A.W.L., B.E.I.), Department of Pharmacology (Y.-H.C., S.K.M., N.L., B.N.D., D.A.B.), Department of Microbiology, Immunology and Cancer Biology, the Center for Cell Clearance, and the Beirne B. Carter Center for Immunology Research (C.B.M., U.M.L., K.S.R.), and Division of Endocrinology (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Biochemistry and Genetics, La Trobe University, Melbourne, Australia (I.K.H.P.); and Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA (I.Z.J.). brant@virginia.edu ravi@virginia.edu.
Kodi S RavichandranFrom the Department of Molecular Physiology and Biophysics, Robert M. Berne Cardiovascular Research Center (M.E.G., J.T.B., L.J.D., A.W.L., B.E.I.), Department of Pharmacology (Y.-H.C., S.K.M., N.L., B.N.D., D.A.B.), Department of Microbiology, Immunology and Cancer Biology, the Center for Cell Clearance, and the Beirne B. Carter Center for Immunology Research (C.B.M., U.M.L., K.S.R.), and Division of Endocrinology (E.B.), University of Virginia School of Medicine, Charlottesville; Department of Biochemistry and Genetics, La Trobe University, Melbourne, Australia (I.K.H.P.); and Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA (I.Z.J.).
La Trobe University · AUTufts Medical Center · USCarter Center · US
Funding
Role of Pannexins in Vascular Smooth Muscle CellsP01HL120840 · NHLBI · UNIVERSITY OF VIRGINIA · PI BAYLISS, DOUGLAS A. · 2014 to 2023
$24.0MBASIC CARDIOVASCULAR RESEARCH TRAINING GRANTT32HL007284 · NHLBI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Brant E Isakson, Gary K Owens · 1985 to 2026
$19.6MTRAINING IN THE PHARMACOLOGICAL SCIENCEST32GM007055 · NIGMS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI LYNCH, KEVIN R. · 1985 to 2022
$7.2MSmooth Muscle Mineralocorticoid Receptors in Vascular Aging and HypertensionR01HL119290 · NHLBI · TUFTS MEDICAL CENTER · PI Iris Z Jaffe · 2014 to 2026
$7.0MTRPM7 at the Crossroads of Tissue Homeostasis and inflammationR01GM108989 · NIGMS · UNIVERSITY OF VIRGINIA · PI DESAI, BIMAL N. · 2016 to 2024
$3.3MPannexin 1 Channels in Cerebral Arterial Myogenic RegulationF32HL131399 · NHLBI · UNIVERSITY OF VIRGINIA · PI GOOD, MIRANDA E · 2016 to 2017
$71kNHLBI NIH HHS F32 HL131399NHLBI NIH HHS P01 HL120840NHLBI NIH HHS R01 HL119290NHLBI NIH HHS T32 HL007284NIGMS NIH HHS R01 GM108989NIGMS NIH HHS T32 GM007055
Abstract
rationaleResistant hypertension is a major health concern with unknown cause. Spironolactone is an effective antihypertensive drug, especially for patients with resistant hypertension, and is considered by the World Health Organization as an essential medication. Although spironolactone can act at the mineralocorticoid receptor (MR; NR3C2), there is increasing evidence of MR-independent effects of spironolactone.
objectiveHere, we detail the unexpected discovery that Panx1 (pannexin 1) channels could be a relevant in vivo target of spironolactone. METHODS AND
resultsFirst, we identified spironolactone as a potent inhibitor of Panx1 in an unbiased small molecule screen, which was confirmed by electrophysiological analysis. Next, spironolactone inhibited α-adrenergic vasoconstriction in arterioles from mice and hypertensive humans, an effect dependent on smooth muscle Panx1, but independent of the MR NR3C2. Last, spironolactone acutely lowered blood pressure, which was dependent on smooth muscle cell expression of Panx1 and independent of NR3C2. This effect, however, was restricted to steroidal MR antagonists as a nonsteroidal MR antagonist failed to reduced blood pressure.
conclusionsThese data suggest new therapeutic modalities for resistant hypertension based on Panx1 inhibition.
Indexed as
AnimalsAntihypertensive AgentsArteriolesConnexinsDiureticsHEK293 CellsHumansHypertensionJurkat CellsMaleMiceMice, Inbred C57BLMiddle AgedMineralocorticoid Receptor AntagonistsNerve Tissue ProteinsSpironolactoneAntihypertensive AgentsConnexinsDiureticsMineralocorticoid Receptor AntagonistsNerve Tissue ProteinsPANX1 protein, humanSpironolactonehypertensionmicemineralocorticoidpannexin 1spironolactonevasoconstriction
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
None linked
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.