An adenosine receptor agonist-induced modulation of TSH-dependent cell growth in FRTL-5 thyroid cells mediated by inhibitory G protein, Gi.
Adenosine has been shown to modulate the TSH-induced DNA synthesis in FRTL-5 thyroid cells. The mechanism of this adenosine action has been somewhat controversial because both A1 adenosine receptor-mediated and non-receptor-mediated mechanisms have been proposed. We have now reexamined our preliminary finding of the inhibitory action of a non-metabolizable adenosine derivative, N6-(L-2-phenylisopropyl)adenosine (PIA), on the TSH-induced DNA synthesis to clarify the adenosine-dependent mechanism of cell growth modulation. PIA dose-dependently inhibited the TSH-induced DNA synthesis expressed by [3H]thymidine incorporation into DNA. This adenosine derivative also prevented the TSH-induced entry of the cell cycle to the S phase at 24 h of culture and the increase in cell number at 48 h. These PIA actions on different aspects of TSH-dependent cell growth were abolished by the treatment of the cells with pertussis toxin, suggesting the involvement of Gi in the PIA action mechanism. Dibutyryl cAMP-induced DNA synthesis was not influenced by PIA. In concert with our previous finding that PIA in a similar concentration range inhibited TSH-induced cAMP production through the adenosine A1 receptor, the present results strongly support the idea that the major pathway of adenosine signaling for the inhibition of the TSH-induced cell proliferation is through the A1 adenosine receptor-Gi system.
Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
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K
Sho
T
T
Narita
F
F
Okajima
Y
Y
Kondo
D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D003994:Bucladesine / Q000378:metabolism / Q000494:pharmacology; D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D016193:G1 Phase; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D037342:Pertussis Toxin; D058906:Purinergic P1 Receptor Agonists; D016192:Resting Phase, Cell Cycle; D016196:S Phase; D013936:Thymidine / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology*; D013972:Thyrotropin / Q000378:metabolism* / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D058906:Purinergic P1 Receptor Agonists; D010566:Virulence Factors, Bordetella; C047235:N-(1-methyl-2-phenylethyl)adenosine; D003994:Bucladesine; D013972:Thyrotropin; D037342:Pertussis Toxin; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D000241:Adenosine; D013936:Thymidine