ArticleMolecular pharmacology2009
Differential effects of selective cyclooxygenase-2 inhibitors on vascular smooth muscle ion channels may account for differences in cardiovascular risk profiles.
Article in Molecular pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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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.
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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
44 citing papers in PubMed, 85 citations in OpenAlex.
- Selective COX-2 inhibition affects fatty acids, but not COX mRNA expression in patients with FAP.Familial cancer · 2010Trial
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- Vasopressin-stimulated ORAI1 expression and store-operated CaJournal of molecular medicine (Berlin, Germany) · 2021Article
- Vascular-Cognitive Impairment following High-Thoracic Spinal Cord Injury Is Associated with Structural and Functional Maladaptations in Cerebrovasculature.Journal of neurotrauma · 2020Article
- The membrane protein KCNQ1 potassium ion channel: Functional diversity and current structural insights.Biochimica et biophysica acta. Biomembranes · 2020Review
- Heteromeric Channels Formed From Alternating Kv7.4 and Kv7.5 α-Subunits Display Biophysical, Regulatory, and Pharmacological Characteristics of Smooth Muscle M-Currents.Frontiers in physiology · 2020Article
- Rationally synthesized coumarin based pyrazolines ameliorate carrageenan induced inflammation through COX-2/pro-inflammatory cytokine inhibition.MedChemComm · 2019Article
- M-type KBritish journal of pharmacology · 2018Review
- Design and Synthesis of Aza-/Oxa Heterocycle-Based Conjugates as Novel Anti-Inflammatory Agents Targeting Cyclooxygenase-2.ACS omega · 2018Article
- Folic acid ameliorates celecoxib cardiotoxicity in a doxorubicin heart failure rat model.Pharmaceutical biology · 2017Article
- Design, Synthesis, and Biological Activity of Tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine Derivatives as Anti-Inflammatory Agents.Molecules (Basel, Switzerland) · 2017Article
- COX-2-selective inhibitors celecoxib and deracoxib modulate transient receptor potential vanilloid 3 channels.British journal of pharmacology · 2017Article
- Staged anticonvulsant screening for chronic epilepsy.Annals of clinical and translational neurology · 2016Article
- New Insights into Mechanisms and Functions of Chemokine (C-X-C Motif) Receptor 4 Heteromerization in Vascular Smooth Muscle.International journal of molecular sciences · 2016Article
- Rigid and remodelled: cerebrovascular structure and function after experimental high-thoracic spinal cord transection.The Journal of physiology · 2016Article
- Heteromerization of chemokine (C-X-C motif) receptor 4 with α1A/B-adrenergic receptors controls α1-adrenergic receptor function.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Evidence of more ion channels inhibited by celecoxib: KV1.3 and L-type Ca(2+) channels.BMC research notes · 2015Article
- Hitting the Bull's-Eye in Metastatic Cancers-NSAIDs Elevate ROS in Mitochondria, Inducing Malignant Cell Death.Pharmaceuticals (Basel, Switzerland) · 2015Review
- Investigation of cyclooxygenase and signaling pathways involved in human platelet aggregation mediated by synergistic interaction of various agonists.Drug design, development and therapy · 2015Article
- Chemokine (C-X-C motif) receptor 4 and atypical chemokine receptor 3 regulate vascular α₁-adrenergic receptor function.Molecular medicine (Cambridge, Mass.) · 2014Article
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5 authors at 1 institution in 1 country.
Funding
Abstract
Celecoxib, rofecoxib, and diclofenac are clinically used cyclooxygenase-2 (COX-2) inhibitors, which have been under intense scrutiny because long-term rofecoxib (Vioxx; Merck, Whitehouse Station, NJ) treatment was found to increase the risk of adverse cardiovascular events. A differential risk profile for these drugs has emerged, but the underlying mechanisms have not been fully elucidated. We investigated the effects of celecoxib, rofecoxib, and diclofenac on ionic currents and calcium signaling in vascular smooth muscle cells (VSMCs) using patch-clamp techniques and fura-2 fluorescence and on arterial constriction using pressure myography. Celecoxib, but not rofecoxib or diclofenac, dramatically enhanced KCNQ (K(v)7) potassium currents and suppressed L-type voltage-sensitive calcium currents in A7r5 rat aortic smooth muscle cells (native KCNQ currents or overexpressed human KCNQ5 currents) and freshly isolated rat mesenteric artery myocytes. The effects of celecoxib were concentration-dependent within the therapeutic concentration range, and were reversed on washout. Celecoxib, but not rofecoxib, also inhibited calcium responses to vasopressin in A7r5 cells and dilated intact or endothelium-denuded rat mesenteric arteries. A celecoxib analog, 2,5-dimethyl-celecoxib, which does not inhibit COX-2, mimicked celecoxib in its enhancement of vascular KCNQ5 currents, suppression of L-type calcium currents, and vasodilation. We conclude that celecoxib inhibits calcium responses in VSMCs by enhancing KCNQ5 currents and suppressing L-type calcium currents, which ultimately reduces vascular tone. These effects are independent of its COX-2 inhibitory actions and may explain the differential risk of cardiovascular events in patients taking different drugs of this class.
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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.