Adenosine has divergent effects on deoxyribonucleic acid synthesis in FRTL5 cells: inhibition of thyrotropin-stimulated and potentiation of insulin-like growth factor-I-stimulated thymidine incorporation.
Adenosine inhibits TSH-stimulated [3H]thymidine incorporation into DNA in FRTL5 thyroid follicular cells by both inhibiting cAMP generation and acting at a locus beyond adenylate cyclase. On the other hand, adenosine markedly potentiates DNA synthesis in FRTL5 stimulated by insulin-like growth factor-I (IGF-I). The mechanisms of this latter effect are unknown, but require the coincubation of adenosine and IGF-I and not mediated by an increase in intracellular cAMP concentration. Adenosine increases the maximal response of FRTL5 to [3H]thymidine incorporation stimulated by IGF-I and increases the sensitivity of FRTL5 to IGF-I. These effects of adenosine are reflected by an increase in nuclear labeling as well as by an increase in [3H]thymidine incorporation into DNA. Adenosine also plays a role as an autocrine growth factor in FRTL5, since adenosine deaminase increases the response of these cells to TSH. The effects of adenosine on both TSH- and IGF-I-stimulated DNA synthesis are shared by guanosine and inosine, although with different potencies for the various guanine nucleosides. Inosine potentiates IGF-I-stimulated DNA synthesis, but inhibits TSH-stimulated DNA synthesis only weakly. Adenosine interacts with multiple receptors and with multiple postreceptor pathways in FRTL5 to produce divergent effects on the control of cell replication by two growth factors (TSH and IGF-I) that act through different postreceptor pathways.
Moses
A C
AC
Charles A. Dana Research Institute, Beth Israel Hospital, Boston, Massachusetts 02215.
Tramontano
D
D
Veneziani
B M
BM
Frauman
A G
AG
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology*; D000243:Adenosine Deaminase / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002460:Cell Line; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis* / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects*; D004357:Drug Synergism; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007700:Kinetics; D013002:Somatomedins / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*; D013972:Thyrotropin / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D013002:Somatomedins; D005576:Colforsin; D003994:Bucladesine; D007334:Insulin-Like Growth Factor I; D013972:Thyrotropin; D004247:DNA; D002772:Cholera Toxin; D000243:Adenosine Deaminase; D000241:Adenosine; D015056:1-Methyl-3-isobutylxanthine; D013936:Thymidine