ACTIVE-TRANSPORT OF NITROFURANTOIN ACROSS A MOUSE MAMMARY EPITHELIAL MONOLAYER

The antibiotic nitrofurantoin is transported against an electrochemica l gradient into milk.A monolayer of CIT3 cells, a subline of the Comma 1D normal mouse mammary epithelial cell line, transports [C-14]-nitro furantoin against a concentration gradient from the basal to the apica l 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 direc tion. Nonlabeled nitrofurantoin (500 mu M) in the basal chamber equali zed the transport in both directions, suggesting that a specific trans porter is responsible for the basal-to-apical increment in flux. From inhibition studies, the apparent affinity of this transporter for nitr ofurantoin is 50 mu M. Changes in pH between 6.4 and 7.8 had no effect on the active transport component of the flux but did affect the pass ive flux component. Passive flux of the nonionized molecule was 2.6 ti mes faster than that of the ionized molecule, but the ionized molecule did appear to cross the membrane passively. Our findings show that ni trofurantoin 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 fo rms of nitrofurantoin cross the membranes of the mammary epithelial ce ll by passive diffusion.