The differential effects of protein kinase C activators and inhibitors on rat anterior pituitary hormone release
The differential effects of protein kinase C activators and inhibitors on rat anterior pituitary hormone release
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蛋白激酶C激活剂和抑制剂对大鼠垂体前叶激素释放的不同影响
DOI：
10.1016/0303-7207(93)90171-f
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发表时间：
1993
影响因子：
4.1
通讯作者：
D. MacEwan
中科院分区：
文献类型：
--
作者：
F. Thomson;Melanie S. Johnson;R. Mitchell;W. Wolbers;A. Ison;D. MacEwan
我们研究了各种蛋白激酶C（PKC）激活剂和抑制剂可能不同地影响体外孵育的大鼠垂体前叶组织中促黄体生成素（LH）和生长激素（GH）释放的可能性。PKC激活剂诱导LH释放的效力顺序为：美泽瑞因>佛波醇12，13-二丁酸酯（PDBu）。Mezerein和PDBu对GH释放的作用是等效的。一系列PKC抑制剂（包括对PKC具有高度选择性的化合物）可有效且完全抑制PKC激活剂诱导的LH和GH释放。白屈菜红碱和1-（5-异喹啉磺酰基）-2-甲基哌嗪二盐酸盐（H7）对PDBu-LH释放的抑制作用弱于对LH释放的抑制作用。PDBu和美泽莱因诱导的LH释放的一个组件被H7以高效力抑制，但检测到第二个H7不敏感的组件。Mezerein和PDBu诱导的GH释放仅由H7抗性组分组成，当通过[3 H]PDBu结合置换研究不同来源的PKC的调节结构域时，对大脑皮质、肺和广泛纯化的脑α和β异构体的PKC，Mezerein的亲和力比PDBu高3-5倍。垂体前叶蛋白激酶C对美泽瑞因和PDBu的亲和力非常接近，这使人联想到它们对GH释放的同等效力，为了研究催化结构域抑制剂H7对不同来源的蛋白激酶C的效力，对来自中脑和垂体前叶的部分纯化的胞浆蛋白激酶C和广泛纯化的蛋白激酶C α和蛋白激酶C β进行了酶活性测定。单独来自垂体前叶的PDBu-induced（磷脂酰丝氨酸依赖性）活性的Ca 2+非依赖性组分显示出异常低的H7抑制效力，但被星形孢菌素和Ro 31-8220有效抑制。相反，H7、staurosporine和Ro-31-8220对垂体前叶中Ca ~（2+）依赖性PKC活性具有抑制作用，其抑制效力与所有其他制剂相同。这些结果与大鼠垂体前叶细胞中存在不同形式的PKC（或PKC样激酶）及其在分泌中的活性作用一致。
We investigated the possibility that various protein kinase C (PKC) activators and inhibitors may differentially affect luteinizing hormone (LH) and growth hormone (GH) release from rat anterior pituitary tissue, incubated in vitro. Activators of PKC induced LH release with the following order of potency: mezerein > phorbol 12,13-dibutyrate (PDBu). Mezerein and PDBu were equipotent on GH release. A range of PKC inhibitors (including compounds highly selective for PKC) potently and completely inhibited PKC activator-induced LH and GH release. Chelerythrine and l-(5-isoquinolinesulfonyI)-2-methylpiperazine dihydrochloride (H7) were less potent inhibitors of PDBu-induced GH release than of LH release. A component of PDBu- and mezerein-induced LH release was inhibited by H7 with high potency, but a second H7-insensitive component was detected. Mezerein- and PDBu-induced GH release consisted of an H7-resistant component only.When the regulatory domain of PKCs from different sources was investigated by displacement of [3H]PDBu binding, the affinity for mezerein was 3–5-fold greater than that for PDBu at PKCs from cerebral cortex, lung and α and β isoforms extensively purified from brain. Anterior pituitary PKCs were unusual in showing closely matched affinity for mezerein and PDBu, reminiscent of their equivalent potency on GH release.In order to investigate the potency of the catalytic domain inhibitor H7 on PKCs from different sources, enzyme activity assays were carried out on partially purified cytosolic PKCs from midbrain and anterior pituitary and on extensively purified PKCα and PKC β. The Ca2+-independent component of PDBu-induced (phosphatidylserinedependent) activity from anterior pituitary alone showed unusually low potency of inhibition by H7 but was potently inhibited by staurosporine and Ro 31-8220. In contrast, the Ca2+-dependent PKC activity in anterior pituitary was inhibited by H7, staurosporine and Ro-31-8220 with high potency as in all other preparations. These results are consistent with the presence and active role in secretion of pharmacologically distinct forms of PKC (or PKC-likekinases) in rat anterior pituitary cells.
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影响因子：
4.8
作者：
J. Turgeon;D. W. Waring
通讯作者：
J. Turgeon;D. W. Waring
附着在 Cytodex 珠上的大鼠垂体前叶细胞的灌注：技术验证。
影响因子：
4.8
作者：
Smith,MA;Vale,WW
通讯作者：
Vale,WW
GH4C1 大鼠垂体细胞中的蛋白激酶 C 异质性。
DOI：
--
发表时间：
1990
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Kiley,S;Schaap,D;Parker,P;Hsieh,LL;Jaken,S
通讯作者：
Jaken,S
来自心脏的磷脂敏感 Ca2 依赖性蛋白激酶。
DOI：
--
发表时间：
1982
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Wise,BC;Glass,DB;Chou,CH;Raynor,RL;Katoh,N;Schatzman,RC;Turner,RS;Kibler,RF;Kuo,JF
通讯作者：
Kuo,JF
佛波酯在含有磷脂酰丝氨酸的 Triton X-100 混合胶束上结合并激活蛋白激酶 C。
DOI：
--
发表时间：
1986
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Hannun,YA;Bell,RM
通讯作者：
Bell,RM