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首页> 外文期刊>American Journal of Physiology >PKA inhibitor, H-89, affects the intracellular transit of regulated secretory proteins in rat lacrimal glands.
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PKA inhibitor, H-89, affects the intracellular transit of regulated secretory proteins in rat lacrimal glands.

机译：PKA抑制剂H-89影响大鼠泪腺中调节分泌蛋白的细胞内转运。

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摘要

We tested the effect of H-89, a protein kinase A (PKA) inhibitor, on the intracellular transit of the regulated secretory proteins in rat lacrimal glands. We show that H-89, by itself, induces the secretion of newly synthesized proteins trafficking in its presence but not of proteins already stored in the mature secretory granules. This secretion does not depend on the presence of extracellular Ca2+. The proteins released are identical to those secreted after cholinergic stimulation or under the action of the ionophore A-23187, but the secretion level is approximately 40% lower. The effect of H-89 seems to be due to PKA inhibition because other protein kinase inhibitors (calphostin C, chelerythrine, H-85) do not induce secretion. We further show that H-89 does not modify the rate of glycoprotein galactosylation but induces the secretion of newly galactosylated glycoproteins. Finally, we used a "20 degrees C block" procedure to show that H-89 affects a trans-Golgi network (TGN) or post-TGN step of the secretory pathway. Our results demonstrate that, in lacrimal cells, H-89 affects the intracellular trafficking of secretory proteins, suggesting a role for PKA in this process.
机译：我们测试了H-89，一种蛋白激酶A（PKA）抑制剂，对大鼠泪腺中调节型分泌蛋白的细胞内转运的作用。我们显示，H-89本身会诱导在其存在下新合成的蛋白质运输的分泌，但不会诱导已经存储在成熟分泌颗粒中的蛋白质的分泌。这种分泌并不取决于细胞外Ca2 +的存在。释放的蛋白质与胆碱能刺激后或在离子载体A-23187的作用下分泌的蛋白质相同，但分泌水平降低了约40％。 H-89的作用似乎是由于PKA抑制所致，因为其他蛋白激酶抑制剂（钙磷蛋白C，白屈菜红碱，H-85）不会诱导分泌。我们进一步表明，H-89不会改变糖蛋白半乳糖基化的速率，但会诱导新的半乳糖基化糖蛋白的分泌。最后，我们使用“ 20度C阻滞”程序显示H-89影响高尔基体反式网络（TGN）或TGN后分泌途径。我们的结果表明，在泪液细胞中，H-89影响分泌蛋白的细胞内转运，提示PKA在此过程中的作用。

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