The Na+-I- cotransporter of the thyroid: characterisation of new inhibitors.
New inhibitors of the Na+-I- cotransporter of the thyroid in bovine thyroid slices and in bovine plasma membrane vesicles have been investigated. They include: (1) econazole; (2) 5-(N,N-hexamethylene)amiloride (HMA); and (3) dysidenin. In both systems, the kinetics of iodide transport yielded apparent Km values of 39 and 14 microM respectively. The possible interaction of each of these inhibitors with the iodide site of the Na+-I- cotransporter was tested by performing detailed transport kinetics analysis at varying iodide concentrations and at 150 mM NaCl. Econazole induced a non-competitive inhibition while dysidenin and HMA gave a mixed type of inhibition. The Ki values for dysidenin and econazole, computed from Dixon plots, were 5 and 2 microM respectively while the Ki value for HMA could not be determined. Each inhibition was reversible, indicating the absence of covalent binding of the inhibitor to the Na+-I- cotransporter.
Vroye
L
L
Laboratory of Bio-Organic Chemistry, Faculty of Sciences, Faculty of Medicine, Université Libre de Bruxelles, B-1070 Brussels, Belgium.
Beauwens
R
R
Van Sande
J
J
Daloze
D
D
Braekman
J C
JC
Golstein
P E
PE
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D004464:Econazole / Q000494:pharmacology; D007454:Iodides / Q000378:metabolism; D007457:Iodine Radioisotopes; D007700:Kinetics; D008081:Liposomes / Q000378:metabolism; D008387:Marine Toxins; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D027981:Symporters; D013844:Thiazoles / Q000494:pharmacology; D013961:Thyroid Gland / Q000378:metabolism*; D000099209:Sodium-Iodide Symporters
D000584:Amiloride; D002352:Carrier Proteins; D004464:Econazole; D007454:Iodides; D007457:Iodine Radioisotopes; D008081:Liposomes; D008387:Marine Toxins; D008565:Membrane Proteins; D027981:Symporters; D013844:Thiazoles; D000099209:Sodium-Iodide Symporters; C057360:5-(N,N-hexamethylene)amiloride; C063771:dysidenin