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Vol. 280, Issue 2, 669-676, 1997
Department of Physiology, 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.
Copyright © by The American Society for Pharmacology and Experimental Therapeutics
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