ArticleBiochemical pharmacology2015
Inhibition of Kv channel expression by NSAIDs depolarizes membrane potential and inhibits cell migration by disrupting calpain signaling.
Article in Biochemical pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.
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
6 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.
- Potassium channels in intestinal epithelial cells and their pharmacological modulation: a systematic review.American journal of physiology. Cell physiology · 2021Pooled it
- Investigation into the Antihypertensive Effects of Diosmetin and Its Underlying Vascular Mechanisms Using Rat Model.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Epigenomic Analysis Reveals the KCNK9 Potassium Channel as a Potential Therapeutic Target for Adenomyosis.International journal of molecular sciences · 2022Article
- Suppression of calpain expression by NSAIDs is associated with inhibition of cell migration in rat duodenum.Toxicology · 2017Article
- Sine-wave electrical stimulation initiates a voltage-gated potassium channel-dependent soft tissue response characterized by induction of hemocyte recruitment and collagen deposition.Physiological reports · 2016Article
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Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Clinical use of non-steroidal anti-inflammatory drugs (NSAIDs) is well known to cause gastrointestinal ulcer formation via several mechanisms that include inhibiting epithelial cell migration and mucosal restitution. The drug-affected signaling pathways that contribute to inhibition of migration by NSAIDs are poorly understood, though previous studies have shown that NSAIDs depolarize membrane potential and suppress expression of calpain proteases and voltage-gated potassium (Kv) channel subunits. Kv channels play significant roles in cell migration and are targets of NSAID activity in white blood cells, but the specific functional effects of NSAID-induced changes in Kv channel expression, particularly on cell migration, are unknown in intestinal epithelial cells. Accordingly, we investigated the effects of NSAIDs on expression of Kv1.3, 1.4, and 1.6 in vitro and/or in vivo and evaluated the functional significance of loss of Kv subunit expression. Indomethacin or NS-398 reduced total and plasma membrane protein expression of Kv1.3 in cultured intestinal epithelial cells (IEC-6). Additionally, depolarization of membrane potential with margatoxin (MgTx), 40mM K(+), or silencing of Kv channel expression with siRNA significantly reduced IEC-6 cell migration and disrupted calpain activity. Furthermore, in rat small intestinal epithelia, indomethacin and NS-398 had significant, yet distinct, effects on gene and protein expression of Kv1.3, 1.4, or 1.6, suggesting that these may be clinically relevant targets. Our results show that inhibition of epithelial cell migration by NSAIDs is associated with decreased expression of Kv channel subunits, and provide a mechanism through which NSAIDs inhibit cell migration and may contribute to NSAID-induced gastrointestinal (GI) toxicity.
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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.