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.

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.
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FRTL-5 甲状腺细胞中 P1-嘌呤能激动剂对促甲状腺素作用的相互调节。

DOI:
10.1016/s0021-9258(18)98877-0
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发表时间:
1991
期刊:
The Journal of biological chemistry
影响因子:
--
通讯作者:
Y. Kondo
Y. Kondo
中科院分区:
--
文献类型:
--
作者:
K. Sho;F. Okajima;M. Abdul Majid;Y. Kondo

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在FRTL-5甲状腺细胞中,促甲状腺激素(TSH)刺激I-外排与磷脂酶C激活和Ca 2+动员。TSH还刺激DNA合成,伴随着cAMP积累。磷脂酶C-Ca 2+途径的显著激活需要10-100 nM TSH,其浓度比刺激cAMP途径所需的浓度高10(3)至10(4)倍。当P1-嘌呤激动剂,苯基异丙基腺苷(PIA)被添加到反应介质中,前者的途径显着增强,而后者的途径被抑制。因此,在PIA的存在下,两种TSH诱导的途径在相似的TSH浓度下被激活。这些PIA作用通过用胰岛活化蛋白(IAP)、百日咳毒素预先处理细胞而完全逆转。当腺苷脱氨酶被添加到反应介质中,TSH诱导的cAMP积累显着增强,这表明腺苷的自分泌作用。在IAP处理的细胞中,TSH诱导的cAMP积累水平达到脱氨酶处理的对照细胞,并且当加入腺苷脱氨酶时没有观察到进一步增加。我们的结论是,在甲状腺,无论是神经或自分泌腺苷信号,介导的IAP敏感的G-蛋白,开关TSH信号转导从cAMP途径的磷脂酶C-Ca 2+途径。
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.
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DOI: --
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