J Korean Med Sci.  2004 Oct;19(5):704-709. 10.3346/jkms.2004.19.5.704.

Theophylline Increases the Uptake of Radioiodine by Mouse Thyroid

• Lee JM
• Caturegli
• Ladenson P

• KMID: 1733513
• DOI: http://doi.org/10.3346/jkms.2004.19.5.704

Abstract

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.

Keyword

Theophylline; Iodine Radioisotopes; Cyclic AMP; Thyroid Gland

MeSH Terms

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

Figure

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  Fig. 1 Kinetics of radioiodine uptake in normal mice. Two C57BL/6j mice for each time point received 5 µCi Na125I in 0.1 mL saline by tail vein injection.

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  Fig. 2 In vivo thyroidal radioiodine uptake.

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  Fig. 3 Radioiodine activity in FRTL-5 cells in response to theophylline.

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  Fig. 4 cAMP concentration in FRTL-5 cells in response to theophylline. Cells were cultured in triplicate (A) or in duplicate (B) with cell concentration of 106 cells/mL in 96-well culture plates. (A) FRTL-5 cells were incubated with 1 µM theophylline for various time periods. (B) Cells were stimulated with various concentrations of theophylline for 30 min.

• 

  Fig. 5 Radioiodine uptake and intracellular cAMP production by FRTL-5 cells in response to serum. FRTL-5 cells were cultured in triplicate in 24-well culture plates to measure radioiodine uptake (A), and in duplicate in 96-well culture plates for cAMP measurement (B).

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