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J. Biol. Chem., Vol. 261, Issue 17, 7640-7643, Jun, 1986
JA Mol, EP Krenning, R Docter, J Rozing and G Hennemann
The role of the rat liver plasma membrane in the regulation of uptake and
subsequent deiodination of thyroxine (T4) or the biologically active
thyroid hormone 3,3',5-triiodothyronine (T3) was investigated. Here we
report on the production of monoclonal antibodies raised against rat
hepatocytes. Two antibodies were selected. Antibody ER-22 did bind to a Mr
52,000 membrane protein and inhibited the 1- and 5-min uptake of both T4
and T3 by primary cultured rat hepatocytes in a dose- dependent fashion. As
the uptake of T4 and T3 depends on the presence of a sodium gradient over
the plasma membrane, the inhibitory potency of ER-22 on the Na+,K+-ATPase
activity was investigated. No inhibition of the uptake of 86Rb+ could be
determined, indicating that antibody ER- 22 is not directed against the
Na+,K+-ATPase but probably the carrier protein itself. Clearance of T3 from
the medium and concomitant iodide production by cultured rat hepatocytes
during a 20-h incubation in the presence of ER-22 were both inhibited by
50% with respect to a control incubation in the absence of monoclonal
antibody, pointing to the importance of carrier-mediated transport in
cellular uptake and metabolism of T3. A second monoclonal antibody did bind
to two other plasma membrane proteins but did not inhibit transport of
thyroid hormone.
Inhibition of iodothyronine transport into rat liver cells by a monoclonal antibody
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