Protein kinase C blocks somatostatin-induced modulation of calcium current in chick sympathetic neurons.
Protein kinase C blocks somatostatin-induced modulation of calcium current in chick sympathetic neurons.
复制标题
蛋白激酶 C 阻断生长抑素诱导的雏鸡交感神经元钙电流调节。
DOI：
10.1152/jn.1993.70.4.1639
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发表时间：
1993
影响因子：
2.5
通讯作者：
Siegelbaum,SA
中科院分区：
文献类型：
--
作者：
Golard,A;Role,LW;Siegelbaum,SA
1. 生长抑素对鸡交感神经元n型Ca2+电流产生电压依赖性抑制。蛋白激酶C （PKC）激活剂预处理鸡交感神经节神经元对钙电流（ICa）无影响，但会降低生长抑素对ICa的抑制作用。2. 生物碱PKC激活剂(-)-吲哚内酰胺V的作用与4 - β - phorl -12-肉豆蔻酸-13-乙酸酯（4 - β - pma）的作用没有明显区别。无活性异构体(+)-吲哚内酰胺V和4 α - pma不改变生长抑素对ICa的调节。3. 生长抑素对ICa的调节使其脱敏，脱敏一半的时间约为3分钟。PKC的激活模拟了正常的脱敏过程，对30 nM生长抑素的反应比1微米生长抑素的反应受到更大程度的抑制。4. PKC似乎在生长抑素受体或受体-G蛋白相互作用水平上起作用，因为PKC的激活不会改变Ca2+电流抑制对GTP的不可水解类似物GTP- γ - s的反应，后者直接激活G蛋白。5. 特异性PKC抑制剂calphostin C在很大程度上逆转了phobol酯的作用，但不会减慢生长抑素反应的正常脱敏率。这表明PKC不参与生长抑素受体的同源脱敏。6. 激活这些细胞中PKC的物质P和另一种PKC激活剂花生四烯酸都没有改变生长抑素对ICa的作用。
1. Somatostatin produces a voltage-dependent inhibition of N-type Ca2+ current in chick sympathetic neurons. Pretreatment of chick sympathetic ganglion neurons with protein kinase C (PKC) activators has no effect on calcium current (ICa) but reduces the inhibition of ICa by somatostatin. 2. The effects of the alkaloid PKC activator (-)-indolactam V were indistinguishable from those of 4 beta-phorbol-12-myristate-13-acetate (4 beta-PMA). The inactive isomers (+)-indolactam V and 4 alpha-PMA did not alter the modulation of ICa by somatostatin. 3. Modulation of ICa by somatostatin desensitizes, with a time for half desensitization of approximately 3 min. PKC activation mimics the normal desensitization process in that responses to 30 nM somatostatin are inhibited to a greater extent than are responses to 1 microM somatostatin. 4. PKC appears to act at the level of the somatostatin receptor or receptor-G protein interaction because PKC activation does not alter Ca2+ current inhibition in response to a nonhydrolyzable analog of GTP, GTP-gamma-S, which directly activates G proteins. 5. The specific PKC inhibitor calphostin C largely reverses the effects of phorbol esters, but does not slow the normal rate of desensitization of somatostatin responses. This indicates that PKC is not involved in the homologous desensitization of the somatostatin receptor. 6. Neither substance P, which activates PKC in these cells, nor arachidonic acid, another PKC activator, altered the action of somatostatin on ICa.