An adenosine receptor agonist-induced modulation of TSH-dependent cell growth in FRTL-5 thyroid cells mediated by inhibitory G protein, G(i)

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 c ontroversial because both A, adenosine receptor-mediated and non-receptor-m ediated mechanisms have been proposed. We have now reexamined our prelimina ry finding of the inhibitory action of a non-metabolizable adenosine deriva tive, N-6-(L-2-phenylisopropyl)adenosine (PIA), on the TSH-induced DNA synt hesis to clarify the adenosine-dependent mechanism of cell growth modulatio n. PIA. dose-dependently inhibited the TSH-induced DNA synthesis expressed by [H-3]thymidine incorporation into DNA. This adenosine derivative also pr evented the TSH-induced entry of the cell cycle to the S phase at 24 h of c ulture and the increase in cell number at 48 h. These PIA actions on differ ent aspects of TSH-dependent cell growth were abolished by the treatment of the cells with pertussis toxin, suggesting the involvement of G(i) in the PIA action mechanism. Dibutyryl cAMP-induced DNA synthesis was not influenc ed by PIA. In concert with our previous finding that PIA in a similar conce ntration range inhibited TSH-induced cAMP production through the adenosine A, receptor, the present results strongly support the idea that the major p athway of adenosine signaling for the inhibition of the TSH-induced cell pr oliferation is through the A, adenosine receptor-G(i) system. (C) Societe f rancaise de biochimie et biologie moleculaire / Elsevier, Paris.