THE NA-I- COTRANSPORTER OF THE THYROID - CHARACTERIZATION OF NEW INHIBITORS()

New inhibitors of the Na+-I(-)cotransporter of the thyroid in bovine t hyroid slices and in bovine plasma membrane vesicles have been investi gated. They include: (1) econazole; (2) 5-(N,N-hexamethylene) amilorid e (HMA); and (3) dysidenin. In both systems, the kinetics of iodide tr ansport yielded apparent K-m values of 39 and 14 mu M respectively. Th e possible interaction of each of these inhibitors with the iodide sit e of the Na+-I(-)cotransporter was tested by performing detailed trans port kinetics analysis at varying iodide concentrations and at 150 mM NaCl. Econazole induced a non-competitive inhibition while dysidenin a nd HMA gave a mixed type of inhibition. The K-i values for dysidenin a nd econazole, computed from Dixon plots, were 5 and 2 mu M respectivel y while the K-i value for HMA could not be determined. Each inhibition was reversible, indicating the absence of covalent binding of the inh ibitor to the Na+-I(-)cotransporter.