Reciprocal modulation of thyrotropin actions by P1-purinergic agonists in FRTL-5 thyroid cells. Inhibition of cAMP pathway and stimulation of phospholipase C-Ca2+ pathway.
In FRTL-5 thyroid cells, thyrotropin (TSH) stimulates I- efflux in association with phospholipase C activation and Ca2+ mobilization. TSH also stimulates DNA synthesis, accompanied by cAMP accumulation. Significant activation of the phospholipase C-Ca2+ pathway requires 10-100 nM TSH a concentration 10(3) to 10(4) times higher than necessary to stimulate the cAMP pathway. When the P1-purinergic agonist, phenylisopropyladenosine (PIA) is added to the reaction medium, the former pathway is markedly enhanced, whereas the latter pathway is inhibited. As a result, in the presence of PIA, both TSH-induced pathways are activated at similar TSH concentrations. These PIA actions are completely reversed by a prior treatment of cells with islet-activating protein (IAP); pertussis toxin. When adenosine deaminase is added to the reaction medium, TSH-induced cAMP accumulation is significantly enhanced, suggesting an autocrine action of adenosine. In IAP-treated cells, the level of TSH-induced cAMP accumulation reaches that of deaminase-treated control cells, and no further increase is observed when adenosine deaminase is added. We conclude that in the thyroid, either an neural or autocrine adenosine signal, mediated by an IAP-sensitive G-protein, switches TSH signal transduction from the cAMP pathway to the phospholipase C-Ca2+ pathway.
Sho
K M
KM
Department of Physical Biochemistry, Gunma University, Maebashi, Japan.
Okajima
F
F
Abdul Majid
M
M
Kondo
Y
Y
D000243:Adenosine Deaminase / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D000242:Cyclic AMP / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D007295:Inositol Phosphates / Q000378:metabolism; D051381:Rats; D011983:Receptors, Purinergic / Q000502:physiology*; D013961:Thyroid Gland / Q000166:cytology / Q000502:physiology*; D013972:Thyrotropin / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism*
D007295:Inositol Phosphates; D011983:Receptors, Purinergic; D013972:Thyrotropin; D004247:DNA; D000242:Cyclic AMP; D010738:Type C Phospholipases; D000243:Adenosine Deaminase; D002118:Calcium