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Inhibition of thyrocyte iodide uptake by H+K+ ATPase inhibitor, timoprazole
1Department of Laboratory Medicine, Kyoto University School of Medicine, Japan.
Abstract:
The inhibitory effect of timoprazole on iodide uptake by cultured thyrocytes was observed using FRTL-5 cells. The inhibition was noticed to be dose dependent and was eliminated completely by rinsing. Timoprazole pretreated with acid had inhibitory effects, but [3H] leucine incorporation experiments indicated that acidified timoprazole inhibited protein synthesis to some degree. In addition, TSH-induced cAMP production was also inhibited by acidified timoprazole. Timoprazole pretreated in a neutral solution did not have any cytotoxic effects on TSH-induced cAMP production or protein synthesis at concentrations less than 1000 microM, suggesting that timoprazole by itself has specific effects on iodide uptake. The absence of any direct interaction of the drug with iodide was confirmed by separation of timoprazole and iodide on a C18 Sep-Pak column. It is concluded that timoprazole by itself could inhibit iodide transport through the thyroid cell membrane. This may provide a useful system in further investigating the mechanism of iodide transport.
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