Protein kinase C inhibits TRH-stimulated phosphoinositide hydrolysis in GH3 cells.
Protein kinase C inhibits TRH-stimulated phosphoinositide hydrolysis in GH3 cells.
复制标题
蛋白激酶 C 抑制 GH3 细胞中 TRH 刺激的磷酸肌醇水解。
DOI：
10.1016/0014-2999(87)90759-x
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发表时间：
1987
影响因子：
5
通讯作者：
Cronin,MJ
中科院分区：
文献类型：
--
作者：
Sortino,M;Canonico,PL;Summers,ST;Cronin,MJ
GH3垂体肿瘤系表达刺激磷酸肌醇水解和激素分泌的TRH受体。通过用[3H]佛波二丁酸酯 (PDB) 直接标记在 GH3 细胞中鉴定出蛋白激酶 C 后，发现佛波酯和 TRH 预处理对随后 TRH 刺激的磷酸肌醇 (IP) 积累的反应具有抑制作用。佛波醇肉豆蔻酸酯乙酸酯 (PMA) 和 PDB 在几分钟内以低 nM 浓度在这方面有效，而不刺激蛋白激酶 C 的佛波醇则没有效果。此外，在 PMA 5 分钟后，IP 的单磷酸盐、双磷酸盐和三磷酸盐形式均平均减少 30-40%。 TRH 浓度-反应研究表明 PMA 引起的 TRH 功效发生明显变化。最后，与 TRH 本身预孵育也能够减少随后对 TRH 的反应。因为 TRH 受体作用被认为通过产生二酰基甘油来激活蛋白激酶 C，所以这些数据表明在 GH3 细胞中连续暴露于 TRH 期间，通过蛋白激酶 C 起作用的负反馈系统。
The GH3pituitary tumor line expresses TRH receptors that stimulate phosphoinositide hydrolysis and hormone secretion. After protein kinase C was identified in GH3cells by direct labeling with [3H]phorbol dibutyrate (PDB), the response to phorbol ester and TRH pretreatment on subsequent TRH-stimulated inositol phosphate (IP) accumulation was found to be inhibitory. Both phorbol myristate acetate (PMA) and PDB were effective in this regard at low nM concentrations within a few minutes, whereas phorbols that do not stimulate protein kinase C were without effect. Furthermore, the mono-, bis- and tris-phosphate forms of IP were all reduced by an average of 30–40% after 5 min of PMA. TRH concentration-response studies indicated a clear change in TRH efficacy induced by PMA. Finally, preincubation with TRH itself was also capable of reducing the subsequent response to TRH. Because TRH receptor action is thought to activate protein kinase C by producing diacylglycerol, these data indicate a negative feedback system via protein kinase C operative during continuous exposure to TRH in GH3cells.