The antifungal antibiotic, clotrimazole, inhibits chloride secretion by human intestinal T84 cells via blockade of distinct basolateral K+ conductances: Demonstration of efficacy in the intact rabbit colon and in an in vivo mouse model of cholera

Journal of Clinical Investigation

Volumn 100, Issue 12, 1997, Pages 3111-3120

  Rufo, Paul A ^a,b   Merlin, Didier ^c,e   Riegler, Martin ^d   Ferguson Maltzman, Margaret H ^a   Dickinson, Bonny L ^a   Brugnara, Carlo ^a,e   Alper, Seth L ^d,e,f   Lencer, Wayne I ^a,e,f  

^a BOSTON CHILDREN S HOSPITAL   (United States)

^b UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

^c BRIGHAM AND WOMEN S HOSPITAL   (United States)

^d BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

^e HARVARD MEDICAL SCHOOL   (United States)

^f HARVARD UNIVERSITY   (United States)

Author keywords

Amphotericin B; Cl secretion; Clotrimazole; K+ channels; Secretory diarrhea

Indexed keywords

AMPHOTERICIN B; CLOTRIMAZOLE; POTASSIUM CHANNEL;

ANIMAL TISSUE; APICAL MEMBRANE; ARTICLE; BASOLATERAL MEMBRANE; CHLORIDE TRANSPORT; CHOLERA; COLON MUCOSA; DIARRHEA; HUMAN; HUMAN CELL; INTESTINE CELL; NONHUMAN; POTASSIUM CONDUCTANCE; POTASSIUM TRANSPORT; PRIORITY JOURNAL; RABBIT;

EID: 0031453854     PISSN: 00219738     EISSN: None     Source Type: Journal    
DOI: 10.1172/JCI119866     Document Type: Article

References (57)

1. Halm, D.R., G.R. Rechkemmer, R.A. Schoumacher, and R.A. Frizzell. 1988. Apical membrane chloride channels in a colonie cell line activated by secretory agonists. Am. J. Physiol. (Cell Physiol. 23). 254:C505-C511.
2. Barrett, K.E. 1993. Positive and negative regulation of chloride secretion in T84 cells. Am. J. Physiol. 265 (Cell Physiol. 34):C859-C868.
3. Halm, D.R., and R.A. Frizzell. 1990. Intestinal chloride secretion. In Textbook of Secretory Diarrhea. E. Lebenthal and M.E. Duffey, editors. Raven Press, Ltd., New York. 47-58.
4. Dharmsathaphorn, K., and J.L. Madara. 1990. Established intestinal cell lines as model systems for electrolyte transport studies. Methods Enzymol. 192: 354-359.
5. Mac Vinish, L.J., R.J. Pickles, and A.W. Cuthbert. 1993. Cyclic AMP and Ca2+ interactions affecting epithelial chloride secretion in human cultured epilhelia. Br. J. Pharmacol. 108:462-468.
6. Madara, J., J. Stafford, K. Dharmsathaphorn, and S. Carlson. 1987. Structural analysis of a human intestinal epithelial cell line. Gastroenterology. 92: 1133-1145.
7. Lomax, R.B., G. Warhurst, and G.I. Sandle. 1996. Characteristics of two basolateral potassium channel populations in human colonie crypts. Gut. 38: 243-247.
8. Rufo, P.A., L. Jiang, S.J. Moe, C. Brugnaru, S.L. Alper, and W.I. Lencer. 1996. The antifungal antibiotic, clotrimazole, inhibits Cl secretion by polarized monolayers of human colonie epithelial cells. J. Clin. Invest. 98:2066-2075.
9. Iliev, I.G., and A.A. Marino. 1993. Potassium channels in epithelial cells. Cell. Mol. Biol. Rev. 39:601-611.
10. Huflejt, M.E., R.A. Blum, S.O. Miller, H.H. Moore, and T.E. Machen. 1994. Regulated Cl transport, K and Cl permeability, and exocytosis in T84 cells. J. Clin. Invest. 93:1900-1910.
11. Mandel, K., J. McRoberts, G. Beuerlein, E. Foster, and K. Dharmsathaphorn. 1986. Ba inhibition of VIP- and A23187-stimulated Cl secretion by T84 cell monolayers. Am. J. Physiol. 259:C486-C494.
12. + channel in colonic secretory cells. Am. J. Physiol. 265:C1271-C1280.
13. Duffey, M., D. Devor, Z. Ahmed, and S. Simasko. 1990. Characterization of a membrane potassium ion conductance in intestinal secretory cells using whole cell patch-clamp and calcium ion-sensitive dye techniques. Methods Enzymol. 192:309-324.
14. Dharmsathaphorn, K., and S.J. Pandol. 1986. Mechanism of chloride secretion induced by carbachol in a colonie epithelial cell line. J. Clin. Invest. 77: 348-354.
15. Devor, D.C., and M.E. Duffey. 1992. Carbachol induces K+, Cl-, and nonselective cation conductances inT84 cells: a perforated patch-clamp study. Am. J. Physiol. (Cell Physiol. 32) 263:C780-C787.
16. + transport and cell dehydration in sickle erythrocytes by clotrimazole and other imidazole derivatives. J. Clin. Invest. 92:520-526.
17. + transport and reverses erythrocyte dehydration in transgenic SAD mice. J. Clin. Invest. 93:1670-1676.
18. Rittenhouse, A.R., D. Vandorpe, C. Brugnara, and S.L. Alper. 1997. The antifungal imidazole clotrimazole and its major in vivo metabolites are potent blockers of the calcium activated potassium channel in murine erythroleu-kemia cells. J. Membr. Biol. In press.
19. Rittenhouse, A.R., C. Parker, C. Brugnara, K.G. Morgan, and S.L. Alper. 1997. Inhibition of maxi-K currents in ferret portal vein smooth muscle cells by the antifungal clotrimazole. Am. J. Physiol. (Cell Physiol.) 273:C45-C56.
20. Brugnara, C., C.C. Armsby, M. Sakamoto, N, Rifai, S.L. Alper, and O. Plait. 1995. Oral administration of clotrimazole and blockade of human erythrocyte Ca++-activated K+ channel: the imidazole ring is not required to inhibitory activity. J. Pharmacol. Exp. Ther. 273:1-7.
21. Brugnara, C., B. Gee, C.C. Armsby, S. Kurth, M. Sakamoto, N. Rifai, S.L. Alper, and O.S. Platt. 1996. Therapy with oral clotrimazole induces inhibition of the gardos channel and reduction of erythrocyte dehydration in patients with sickle cell disease. J. Clin. Invest. 97:1227-1234.
22. Wong, S.M., A. Tesfaye, M.C. DeBell, and H.S. Chase. 1990 Carbachol increases basolateral K+ conductances in T84 cells. J. Gen. Physiol. 96:1271-1285.
23. Merlin, D., X. Guo, C.L. Laboisse, and U. Hopfer. 1995. Ca2+ and cAMP activate different K+ conductances in the human intestinal goblet cell line HT29-Cl,16E. Am. J. Physiol. (Cell Physiol. 37)268:C1503-C1511.
24. Fischer, H., M. Kreusel, B. Illek, T. Machen, V. Hegel, and W. Clauss, 1992. The outwardly rectifying Cl-channel is not involved in cAMP-mediated Cl-secretion in HT-29 cells: evidence for a very low conductance Cl-channel. Pflugers Arch. 422:159-167.
25. Lencer, W.L., C. Delop, M.R. Neutra, and J.L. Madara. 1992. Mechanism of cholera toxin action on polarized epithelial human epithelial cell line: role of vesicular traffic. J. Cell Biol. 117:1197-1209.
26. Lencer, W.L., J.B. de Almeida, S. Moe, J.L. Stow, D.A. Ausiello, and J.L. Madara. 1993. Entry of cholera toxin into polarized human intestinal epithelial cells: identification of an early brefeldin A sensitive event required for A1-peptide generation. J. Clin. Invest. 92:2941-2951.
27. Kirk, K.L., and D.C. Dawson. 1983. Basolateral potassium channel in turtle colon. Evidence for single-file ion flow. J. Gen. Physiol. 83:297-329.
28. Grass, G.M., and S.A. Sweetana. 1988. In vitro measurements of gastrointestinal tissue permeability using a new diffusion cell. Pharmacol. Res. 5: 372-376.
29. Feil, W., E. Lacy, Y.M. Wong, D. Burger, E. Wenzl, M. Starlinger, and R. Schiessel. 1989. Rapid epithelial restitution of the human and rabbit colonie mucosa. Gastroenterology. 97:685-701.
30. Riegler, M., T. Sedivy, T. Sogukoglu, E. Consentini, G. Bischof, B. Teleky, W. Feil, R. Schiessel, G. Hamilton, and E. Wenzl. 1996. Epidermal growth factor promotes rapid response to epithelial injury in rabbit duodenum in vitro. Gastroenterology. 111:28-36.
31. Riegler, M., R. Sedivy, C. Pothoulakis, G. Hamilton, J. Zacherl, G. Bischof, E. Consentini, W. Feil, R. Schiessel, J.T. LaMont, and E. Wenzl. 1995. Clostridium difficile toxin B is more potent than toxin A in damaging human colonie epithelium in vitro. J. Clin. Invest. 95:2004-2011.
32. - secretion in a model intestinal epithelium induced by a neutrophil-derived secretagogue. J. Clin. Invest. 89:1938-1944.
33. Powell, D.W. 1981. Barrier function of epithelia. Am. J. Physiol. (Gustrointest. Liver Physiol.)241:G275-G288.
34. Tabcharani, J., A. Boucher, J. Eng, and J. Hanrahan. 1994. Regulation of inwardly rectifying K channel in the T84 epithelial cell line by calcium, nucleotides, and kinases. J. Membr. Biol. 142:255-266.
35. Reenstra, W. 1993. Inhibition of cAMP- and Ca-dependent Cl-secretion by phorbol esters: inhibition of basolateral K+ channels. Am. J. Physiol 264:C161-C168.
36. McRoberts, J., G. Beuerlein, and K. Dharmsathaphorn. 1985. Evidence for cAMP and Ca activated K channels in a human colonic epithelial cell line. Fed. Proc. 44:646a.
37. Cartwright, C., J. McRoberts, K. Mandel, and K. Dharmsathaphorn. 1985. Synergistic action of cyclic adenosine monophosphate- and calcium-mediated chloride secretion in a colonic epithelial line. J. Clin. Invest. 76:1837-1842.
38. Tousson, A., C.M. Fuller, and D.J. Benos. 1996. Apical recruitment of CFTR in T-84 cells is dependent on cAMP and microtubules but not Ca2+ or microfilaments. J. Cell Sci. 109:1325-1334.
39. Sears, C.L., F. Firoozmand, A. Mellander, F.G. Chambers, I.G. Eromar, A.G. Bot, B. Scholte, H.R. De Jonge, and M. Donowitz. 1995. Genestein and tyrphostin 47 stimulate CFTR-mediated Cl-secretion in T84 cell monolayers. Am. J. Physiol. 269:G874-G882.
40. - secretion by benzimidazolones. II. Coordinate regulation of apical GCl and basolateral GK. Am. J. Physiol. 271:L785-L795.
41. Devor, D.C., S.M. Simasko, and M.E. Duffey. 1990. Carhacol induces oscillations of membrane potassium conductance in a colonie cell line, T84. Am. J. Physiol. (Cell Physiol. 27). 258:C318-C326.
42. Weuta, H. 1974. Clinical studies with oral clotrimazole. Postgrad. Med. J. 50(suppl.):45-48.
43. Sawyer, P.R., R.N. Brogden, R.M. Pinder, T.M. Speight, and G.S. Avery. 1975. Clotrimazole: a review of its antifungal activity and therapeutic efficacy. Drugs. 9:424-447.
44. Moshe, M., L. Boxall, and E.W. Gelfand. 1977. Clotrimazole: intermittant therapy in chronic mucocutaneous candidiasis. Am. J. Dis. Child. 313:305-307.
45. Leikin, S., R. Parrott, and J. Randolph. 1976. Clotrimazole treatment of chronic mucocutaneous candidiasis. J. Pediatr. 88:864-866.
46. Haller, I. 1980. Imidazole-antimycotics: experience with Clotrimazole, experimental aspects, aims for the future. In Medical Mycology. H.J. Preusser, editor. Gustav Fischer Verlag, New York. 241-251.
47. Ginsburg, C.H., G.L. Braden, A.I. Tauber, and J.S. Trier. 1981. Oral clotrimazole in the treatment of esophageal candidiasis. Am. J. Med. 71:891-895.
48. Capedevila, J., L. Gil, M. Orellana, L.J. Marnetl, J.I. Mason, P. Yadgiri, and R. Falck. 1988. Inhibitors of cytochrome P-450-dependent arachadonic acid metabolism. Arch. Biochem. Biophys. 261:257-263.
49. Wang, W.H., M. Lu, and S.C. Hebert. 1996. Cytochrome P-450 metabolites mediate extracellular Ca(2+)-induced inhibition of apical K+ channels in the TAL. Am. J. Physiol. 271:C103-C111.
50. Brugnara, C., C.C. Armsby, M. Sakamoto, N. Rifai, S. Alper, and O. Platt. 1995. Oral administration of Clotrimazole and blockade of human erythrocyte Ca++-activated K+ channels: the imidazole ring is not required for inhibitory activity. J. Pharmacol. Exp. Ther. 273:266-272.
51. Bennett, J.E. 1990. Antifungal agents. In The Pharmacological Basis of Therapeutics. A.G. Goodman, T.W. Rall, A.S. Nies, and P. Taylor, editors. Pergamon Press, New York. 1169-1177.
52. Lohrmann, E., I. Burhoff, B. Nitschke, H.J. Lang, D. Mania, H.C. Englert, M. Hropot, R. Warth, W. Rohm, M. Bleich, and R. Greger, 1995. A new class of inhibitors of cAMP-mediated Cl-secretion in rabbit colon, acting by the reduction of cAMP-activated K+ conductance. Pflugers Arch. 429:517-530.
53. Warth, R.N., N. Riedmann, M. Bleich, W. Van Driessche, A.E. Busch, and R. Greger. 1996. The cAMP-regulated and 293B-inhibited K conductance of rat colonic crypt base cells. Pflugers Arch. 432:81-88.
54. Brugnara, C., L. De Franceschi, and S.L. Alper. 1993. Ca2+-activated K+ transport of human and rabbit erythrocytes: comparison of binding and transport inhibition by scorpion toxins. J. Biol. Chem. 268:8760-8768.
55. Rittenhouse, A.R., C. Brugnara, and S.L. Alper. 1994. Clotrimazole, a blocker of calcium-activated K+ channels. Biophys. J. 66:209a. (Abstr.)
56. Bleich, M., N. Riedmann, R. Warth, D. Kerstan, J. Leipziger, M. Hor, W. Van Driessche, and R. Greger. 1996. Ca2+-regulated K and non-selective cation channels in the basolaleral membrane of the rat colonie crypt base cells. Pflugers Arch. 432:1011-1022.
57. Bachman, K. 1992. The effects of cobalt chloride, SKF-525F, and N-(3,5-dichlorophenyl)succinimide on in vivo hepatic mixed function oxidase activity as determined by single-sample plasma clearances. Xenobiotica. 22:27-31.