ArticleThe Journal of clinical investigation1996
The antifungal antibiotic, clotrimazole, inhibits Cl- secretion by polarized monolayers of human colonic epithelial cells.
Article in The Journal of clinical investigation, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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
19 citing papers in PubMed, 65 citations in OpenAlex.
- Role of SNARE Proteins in the Insertion of KCa3.1 in the Plasma Membrane of a Polarized Epithelium.Frontiers in physiology · 2022Article
- Intestinal epithelial potassium channels and CFTR chloride channels activated in ErbB tyrosine kinase inhibitor diarrhea.JCI insight · 2019Article
- Vibrio cholerae ensures function of host proteins required for virulence through consumption of luminal methionine sulfoxide.PLoS pathogens · 2017Article
- 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
- Anterograde trafficking of KCa3.1 in polarized epithelia is Rab1- and Rab8-dependent and recycling endosome-independent.PloS one · 2014Article
- The Epac1 signaling pathway regulates Cl- secretion via modulation of apical KCNN4c channels in diarrhea.The Journal of biological chemistry · 2013Article
- Trafficking of intermediate (KCa3.1) and small (KCa2.x) conductance, Ca(2+)-activated K(+) channels: a novel target for medicinal chemistry efforts?ChemMedChem · 2012Review
- Cyclic AMP-induced K+ secretion occurs independently of Cl- secretion in rat distal colon.American journal of physiology. Cell physiology · 2012Article
- Characteristics of Kcnn4 channels in the apical membranes of an intestinal epithelial cell line.American journal of physiology. Gastrointestinal and liver physiology · 2011Article
- Lack of Restoration in Vivo by K-Channel Modulators of Jejunal Fluid Absorption after Heat Stable Escherichia coli Enterotoxin (STa) Challenge.Journal of tropical medicine · 2011Article
- Mucosal potassium efflux mediated via Kcnn4 channels provides the driving force for electrogenic anion secretion in colon.American journal of physiology. Gastrointestinal and liver physiology · 2010Article
- Cloning and identification of tissue-specific expression of KCNN4 splice variants in rat colon.American journal of physiology. Cell physiology · 2010Article
- Recycling of the Ca2+-activated K+ channel, KCa2.3, is dependent upon RME-1, Rab35/EPI64C, and an N-terminal domain.The Journal of biological chemistry · 2010Article
- Therapeutic potential of KCa3.1 blockers: recent advances and promising trends.Expert review of clinical pharmacology · 2010Article
- K+ channel modulators for the treatment of neurological disorders and autoimmune diseases.Chemical reviews · 2008Review
- Vibrio cholerae infection of Drosophila melanogaster mimics the human disease cholera.PLoS pathogens · 2005Article
- Anthrax toxin entry into polarized epithelial cells.Infection and immunity · 1999Article
- 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.The Journal of clinical investigation · 1997Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Clotrimazole (CLT) prevents dehydration of the human HbSS red cell through inhibition of Ca++-dependent (Gardos) K+ channels in vitro (1993. J. Clin Invest. 92:520-526.) and in patients (1996. J. Clin Invest. 97:1227-1234.). Basolateral membrane K+ channels of intestinal crypt epithelial cells also participate in secretagogue-stimulated Cl- secretion. We examined the ability of CLT to block intestinal Cl- secretion by inhibition of K+ transport. Cl- secretion was measured as short-circuit current (Isc) across monolayers of T84 cells. CLT reversibly inhibited Cl- secretory responses to both cAMP- and Ca2+-dependent agonists with IC50 values of approximately 5 microM. Onset of inhibition was more rapid when CLT was applied to the basolateral cell surface. Apical Cl- channel and basolateral NaK2Cl cotransporter activities were unaffected by CLT treatment as assessed by isotopic flux measurement. In contrast, CLT strongly inhibited basolateral 86Rb efflux. These data provide evidence that CLT reversibly inhibits Cl- secretion elicited by cAMP-, cGMP-, or Ca2+-dependent agonists in T84 cells. CLT acts distal to the generation of cAMP and Ca2+ signals, and appears to inhibit basolateral K+ channels directly. CLT and related drugs may serve as novel antidiarrheal agents in humans and animals.
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