Functional regulation of GTP-binding protein coupled to insulin-like growth factor-I receptor by lithium during G1 phase of the rat thyroid cell cycle.
The regulatory effects of lithium on the function of pertussis toxin-sensitive GTP-binding (G(i))-proteins located on the mitogenic pathway activated by insulin-like growth factor-I (IGF-I) in FRTL-5 cells were studied. Addition of GTP-gamma-S to the thyroid stimulating hormone-primed cell membranes resulted in a decreased affinity of IGF-I receptor binding, and the dissociation constant (Kd) increased from 0.46 nM to 3.1 nM. Moreover, IGF-I stimulated GTP-gamma-S binding to a 40-kDa protein, and pertussis toxin (PT) attenuated the stimulatory effect of IGF-I on the same protein. Lithium lowered the affinity of IGF-I receptor binding and the Kd (3.4 nM) was in the same range as that in the presence of GTP-gamma-S. The inhibitory effect of lithium was markedly abolished by pretreatment with PT. Lithium attenuated the amounts of ADP-rebosylation of the 40-kDa protein by PT. In addition, lithium stimulated Ca2+ entry, similar to that by IGF-I, and induced cell proliferation via a PT-sensitive step. These findings suggest that lithium may be capable of modulating the function of G(i)-proteins coupled to IGF-I receptors during the G1 phase of the FRTL-5 cell cycle.
Department of Laboratory Medicine, Osaka University Medical School, Japan.
K
K
Takada
H
H
Tada
T
T
Takano
S
S
Nishiyama
N
N
Amino
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002712:Chlorides / Q000494:pharmacology*; D016193:G1 Phase / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology; D008094:Lithium / Q000494:pharmacology*; D018021:Lithium Chloride; D037342:Pertussis Toxin; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D013961:Thyroid Gland / Q000166:cytology* / Q000187:drug effects; D013972:Thyrotropin / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D002712:Chlorides; D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D007334:Insulin-Like Growth Factor I; D013972:Thyrotropin; D008094:Lithium; D037342:Pertussis Toxin; D017526:Receptor, IGF Type 1; D019204:GTP-Binding Proteins; D018021:Lithium Chloride