Extracellular adenosine increases Na+/I- symporter gene expression in rat thyroid FRTL-5 cells.
We studied the effect of extracellular adenosine on iodide (I-) transport in FRTL-5 thyroid cells. I- accumulation increases after a 48 h exposure to adenosine in a concentration-dependent manner, reaching a maximum of 7.9-fold basal levels at 72 h after the addition of 300 microM adenosine. Neither I- efflux nor intracellular cyclic adenosine monophosphate accumulation is affected by the exposure to adenosine. The stimulation of I- transport by adenosine is partly as a result of an increase in Na+/I- symporter (NIS) mRNA and protein levels. Northern blot analysis revealed that adenosine increases NIS mRNA levels at 24 h, reaching a maximum at 36 h. Western blot analysis demonstrated that adenosine increases NIS protein levels at 36 h, reaching a maximum at 72 h, in parallel with the kinetics of adenosine-induced I- transport. Adenosine increased the promoter activity of a full-length NIS promoter-luciferase chimera, suggesting that the effect of adenosine on NIS mRNA levels is transcriptional. The stimulatory effect of adenosine on NIS mRNA levels, is mimicked by N6-(L-2-phenylisopropyl) adenosine (PIA), an A1 adenosine receptor agonist, and inhibited by 1,3-dipropyl-8-cyclopentylxanthine, an A1 adenosine receptor antagonist, suggesting that the effect is mediated via the A1 adenosine receptor stimulation in FRTL-5 cells. Incubating cells with islet-activating protein inhibited the adenosine-induced NIS mRNA levels. In sum, extracellular adenosine increases NIS gene expression and stimulates I- transport via the A1 adenosine receptor-Gi/Go protein signal transduction pathway.
Harii
N
N
The Third Department of Internal Medicine, Yamanashi Medical University, Tamaho, Japan.
Endo
T
T
Ohmori
M
M
Onaya
T
T
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000235:genetics*; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D007455:Iodine / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics*; D037342:Pertussis Toxin; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000187:drug effects; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D027981:Symporters; D013961:Thyroid Gland / Q000166:cytology*; D013972:Thyrotropin / Q000235:genetics / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000378:metabolism / Q000494:pharmacology; D000099209:Sodium-Iodide Symporters
D000241:Adenosine; D002352:Carrier Proteins; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D007455:Iodine; D008565:Membrane Proteins; D037342:Pertussis Toxin; D012333:RNA, Messenger; D018047:Receptors, Purinergic P1; D027981:Symporters; D013972:Thyrotropin; D010566:Virulence Factors, Bordetella; D000099209:Sodium-Iodide Symporters