ArticleThe Journal of clinical investigation1997
The antifungal antibiotic, clotrimazole, inhibits chloride secretion by human intestinal T84 cells via blockade of distinct basolateral K+ conductances. Demonstration of efficacy in intact rabbit colon and in an in vivo mouse model of cholera.
Article in The Journal of clinical investigation, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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
44 citing papers in PubMed, 117 citations in OpenAlex.
- Mg2+ supplementation treats secretory diarrhea in mice by activating calcium-sensing receptor in intestinal epithelial cells.The Journal of clinical investigation · 2024Article
- Lubiprostone is non-selective activator of cAMP-gated ion channels and Clc-2 has a minor role in its prosecretory effect in intestinal epithelial cells.Molecular pharmacology · 2022Article
- Repurposing calcium-sensing receptor agonist cinacalcet for treatment of CFTR-mediated secretory diarrheas.JCI insight · 2021Article
- Cyclic AMP-Dependent Regulation of Kv7 Voltage-Gated Potassium Channels.Frontiers in physiology · 2020Review
- KCa3.1 Transgene Induction in Murine Intestinal Epithelium Causes Duodenal Chyme Accumulation and Impairs Duodenal Contractility.International journal of molecular sciences · 2019Article
- Intestinal epithelial potassium channels and CFTR chloride channels activated in ErbB tyrosine kinase inhibitor diarrhea.JCI insight · 2019Article
- Enterocyte KThe Journal of physiology · 2018Article
- The Role of Ion Transporters in the Pathophysiology of Infectious Diarrhea.Cellular and molecular gastroenterology and hepatology · 2018Review
- Vibrio cholerae ensures function of host proteins required for virulence through consumption of luminal methionine sulfoxide.PLoS pathogens · 2017Article
- Structural Insights into the Atomistic Mechanisms of Action of Small Molecule Inhibitors Targeting the KCa3.1 Channel Pore.Molecular pharmacology · 2017Article
- Pathogen-induced secretory diarrhea and its prevention.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2016Review
- Article
- Shikonin Inhibits Intestinal Calcium-Activated Chloride Channels and Prevents Rotaviral Diarrhea.Frontiers in pharmacology · 2016Article
- Electrophysiological Studies into the Safety of the Anti-diarrheal Drug Clotrimazole during Oral Rehydration Therapy.PLoS neglected tropical diseases · 2015Article
- Secretory diarrhoea: mechanisms and emerging therapies.Nature reviews. Gastroenterology & hepatology · 2015Review
- Blood-brain barrier KCa3.1 channels: evidence for a role in brain Na uptake and edema in ischemic stroke.Stroke · 2015Article
- Molecular mechanisms of calcium-sensing receptor-mediated calcium signaling in the modulation of epithelial ion transport and bicarbonate secretion.The Journal of biological chemistry · 2014Article
- Inhibition of cAMP-activated intestinal chloride secretion by diclofenac: cellular mechanism and potential application in cholera.PLoS neglected tropical diseases · 2014Article
- The in vitro and in vivo antitumor effects of clotrimazole on oral squamous cell carcinoma.PloS one · 2014Article
- The Epac1 signaling pathway regulates Cl- secretion via modulation of apical KCNN4c channels in diarrhea.The Journal of biological chemistry · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The antifungal antibiotic clotrimazole (CLT) blocks directly and with high potency the Ca2+-activated K+ channels of human erythrocytes, erythroleukemia cells, and ferret vascular smooth muscle cells. We recently reported that CLT inhibits Cl- secretion in human intestinal T84 cells, likely by affecting K+ transport (Rufo, P.A., L. Jiang, S.J. Moe, C. Brugnara, S.L. Alper, and W.I. Lencer. 1996. J. Clin. Invest. 98:2066-2075). To determine if CLT had direct effects on K+ conductances in T84 cells, we selectively permeabilized apical membranes of confluent T84 cell monolayers using the ionophore amphotericin B. This technique permits direct measurement of basolateral K+ transport. We found that CLT and a stable des-imidazolyl derivative inhibited directly two pharmacologically distinct basolateral membrane K+conductances, but had no effect on apical membrane Cl- conductances. The effects of CLT on Cl- secretion were also examined in intact tissue. CLT inhibited forskolin-induced Cl- secretion in rabbit colonic mucosal sheets mounted in Ussing chambers by 91%. CLT also inhibited cholera toxin-induced intestinal Cl- secretion in intact mice by 94%. These data provide direct evidence that CLT blocks Cl- secretion in intestinal T84 cells by inhibition of basolateral K+ conductances, and show that CLT inhibits salt and water secretion from intact tissue in vitro and in vivo. The results further support the suggestion that CLT and its metabolites may show clinical efficacy in the treatment of secretory diarrheas of diverse etiologies.
Indexed as
Identifiers
What OpenQuestion holds
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.