Diagnostic and therapeutic use of radioiodine in the management of thyroid disorders depends on the ability of thyroid cells to concentrate radioiodine, a process that is regulated by the intracellular increase in cAMP. We hypothesized that theophylline, a drug known to increase intracellular cAMP via inhibition of phosphodiesterase, could increase thyroidal radioiodine uptake. We tested this effect in vivo, using C57BL/6j mice, and in vitro, using Fisher rat thyroid (FRTL-5) cells. One mouse received 2.5mg theophylline i.p., whereas a control mouse received only saline. Twenty-hours after theophylline, mice were injected with 10mu Ci Na(125)I in 0.1 mL saline through the tail vein. Mean thyroidal (125)I activity was 3.3-fold higher in theophylline-treated mice than in their respective controls. Radioiodine uptake and intracellular cAMP production of FRTL-5 cells were increased by a relatively low concentration of theophylline (1mu M). Intracellular cAMP increased up to 30 min and then declined in response to 1mu M theophylline. Sera from theophylline-treated mice stimulated (125)I uptake and intracellular cAMP production by FRTL-5 cells. These findings show that theophylline can enhance radioiodine uptake by thyrocytes in vivo and in vitro. The in vitro effects of theophylline on both radioiodine uptake and cAMP production in a dose-dependent manner are consistent with an action mediated by phosphodiesterase inhibition.
Animals ; Blood Proteins/pharmacology ; Cells, Cultured ; Cyclic AMP/metabolism ; Female ; Iodine Radioisotopes/*diagnostic use/pharmacokinetics ; Mice ; Mice, Inbred C57BL ; Theophylline/*pharmacology ; Thyroid Gland/cytology/*metabolism ; Vasodilator Agents/*pharmacology