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OtherDRUG METABOLISM AND DISPOSITION

Active Transport of Nitrofurantoin Across a Mouse Mammary Epithelial Monolayer

Villi S. Toddywalla, Frank W. Kari and Margaret C. Neville
Journal of Pharmacology and Experimental Therapeutics February 1997, 280 (2) 669-676;
Villi S. Toddywalla
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Frank W. Kari
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Margaret C. Neville
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Abstract

The antibiotic nitrofurantoin is transported against an electrochemical gradient into milk.A monolayer of CIT3 cells, a subline of the Comma 1D normal mouse mammary epithelial cell line, transports [14C]-nitrofurantoin against a concentration gradient from the basal to the apical solution when grown on membrane filters. In a side-by-side diffusion chamber with well-stirred solutions on both sides, the transfer rate is 50% higher in the basal-to-apical than in the apical-to-basal direction. Nonlabeled nitrofurantoin (500 μM) in the basal chamber equalized the transport in both directions, suggesting that a specific transporter is responsible for the basal-to-apical increment in flux. From inhibition studies, the apparent affinity of this transporter for nitrofurantoin is 50 μM. Changes in pH between 6.4 and 7.8 had no effect on the active transport component of the flux but did affect the passive flux component. Passive flux of the nonionized molecule was 2.6 times faster than that of the ionized molecule, but the ionized molecule did appear to cross the membrane passively. Our findings show that nitrofurantoin is actively transported across a mammary epithelial cell monolayer by a transporter whose affinity for nitrofurantoin does not depend on the anionic charge on nitrofurantoin. The pH dependence of a parallel passive pathway suggests that both nonionized and ionized forms of nitrofurantoin cross the membranes of the mammary epithelial cell by passive diffusion.

Footnotes

  • Send reprint requests to: Margaret C. Neville, Ph.D., Department of Physiology, Box C240, University of Colorado Health Sciences Center, Denver, CO 80262.

  • ↵1 The work presented here was supported in part by NIH grant HD 19547 to M.C.N. and by a Research Fellowship from the World Health Organization to V.S.T.

  • Abbreviations:
    CIT3
    a subline of the Comma 1D normal mouse mammary cell line
    EGF
    epithelial growth factor
    • Received July 8, 1996.
    • Accepted October 3, 1996.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 280, Issue 2
1 Feb 1997
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OtherDRUG METABOLISM AND DISPOSITION

Active Transport of Nitrofurantoin Across a Mouse Mammary Epithelial Monolayer

Villi S. Toddywalla, Frank W. Kari and Margaret C. Neville
Journal of Pharmacology and Experimental Therapeutics February 1, 1997, 280 (2) 669-676;

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OtherDRUG METABOLISM AND DISPOSITION

Active Transport of Nitrofurantoin Across a Mouse Mammary Epithelial Monolayer

Villi S. Toddywalla, Frank W. Kari and Margaret C. Neville
Journal of Pharmacology and Experimental Therapeutics February 1, 1997, 280 (2) 669-676;
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