Inhibition of the Na+/I‐ symporter by harmaline and 3‐amino‐1‐methyl‐5H‐pyrido(4,3‐b)indole acetate in thyroid cells and membrane vesicles

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Abstract
Novel inhibitors of the Na+/I− symporter were identified using rat‐thyroid‐derived FRTL‐5 cells and sealed vesicles from calf thyroid as model systems. Na+‐dependent 125I− uptake was inhibited by the hallucinogenic drug harmaline and by a chemically related convulsive agent, 3‐amino‐1‐methyl‐5H‐pyrido(4,3‐b)indole acetate (TRP‐P‐2). TRP‐P‐2 (Ki= 0.25 mM) was tenfold more effective as an inhibitor than harmaline (Ki= 4.0 mM). Inhibition by TRP‐P‐2 was competitive with respect to Na+ and was fully reversible. Although TRP‐P‐2 is a Inhibitively low‐affinity inhibitor, its affinity for the Na+ site of the Na+/I− symporter is over 100 times higher than that of Na+ (Km= 50 mM). 45Ca2+‐efflux rates in calf thyroid membrane vesicles were not affected by TRP‐P‐2, indicating that membrane integrity is not disrupted by the drug. These findings show that TRP‐P‐2 may be a potentially useful tool for the identification and characterization of the Na+/I− symporter.