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Stimulation of sodium transport by duramycin in cultured human colonic epithelia.

Authors
Type
Published Article
Journal
Journal of Pharmacology and Experimental Therapeutics
0022-3565
Publisher
American Society for Pharmacology & Experimental Therapeutics
Publication Date
Volume
259
Issue
3
Pages
1050–1058
Identifiers
PMID: 1762061
Source
Medline

Abstract

Effects of two peptide antibiotics, duramycin and Ro 09-0198, on ion transport in cultured human colonic epithelia were investigated. Both peptides acted on the apical face of epithelial monolayers, causing an increase in ion transport measured as short circuit current. Concentration-response relationships were complex, because above a concentration of 2 to 5 microM, the peptides caused currents either to decline toward zero or become large and unstable. Ion substitution experiments showed that the majority of the current response was due to electrogenic sodium absorption. An outward chloride current could also be induced by duramycin, provided an outwardly directed chloride gradient was imposed. It was also shown that the peptides could increase [Ca]i, probably by creating entry sites in the apical face. Duramycin was also able to create large conductance (2000 pS) channels in "black" lipid bilayers. It is proposed that the antibiotics interact with membrane lipids in the apical faces of colonic epithelia to create artificial nonspecific ion channels. The prevailing electrochemical gradients which exist when the epithelia are bathed symmetrically in Krebs-Henseleit solution result in increased electrogenic sodium transport. No evidence was found for colonic epithelia that duramycin or Ro 09-0198 interacted specifically with either membrane channels or receptors to increase ion transport.

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