ARACHIDONIC-ACID STIMULATES INTRACELLULAR CALCIUM MOBILIZATION AND REGULATES PROTEIN-SYNTHESIS, ATP LEVELS, AND MUCIN SECRETION IN SUBMANDIBULAR-GLAND CELLS
ARACHIDONIC-ACID STIMULATES INTRACELLULAR CALCIUM MOBILIZATION AND REGULATES PROTEIN-SYNTHESIS, ATP LEVELS, AND MUCIN SECRETION IN SUBMANDIBULAR-GLAND CELLS
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DOI：
10.1177/00220345950740060901
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发表时间：
1995-06-01
影响因子：
7.6
通讯作者：
MELLOW, L
中科院分区：
文献类型：
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作者：
FLEMING, N;MELLOW, L
早前观察到花生四烯酸抑制大鼠颌下腺泡细胞膜肌醇磷脂的合成，促使本研究探讨该脂肪酸是否也可能调节模型中的其他关键生理过程。花生四烯酸在浓度高于10 μ mol/L时，可抑制腺泡细胞高达97%的蛋白质合成。这种酸还通过一种不敏感的机制将细胞ATP水平降低到控制值的25%。在通透性细胞的内质网钙研究中，花生四烯酸刺激了高达73%负载的ER-Ca-45（2+）向细胞质的动员，比其他钙易位子、素或肌醇1,4,5-三磷酸引起的反应要大得多。此外，花生四烯酸酯刺激完整细胞中超过80%的细胞总Ca-45（2+）释放到细胞外间隙，并刺激下颌下模型中的粘蛋白分泌。花生四烯酸对蛋白质合成的抑制作用被碳醇、塔素素和BAPTA/AM复制，这三种药物通过不同的机制引起ER-Ca2+的净外排。此外，与花生四烯酸酯对ATP的作用相比，碳醇和素也显著降低了细胞内核苷酸的水平。综上所述，花生四烯酸可调节大鼠颌下腺粘液腺泡细胞的中枢合成/分泌过程，并提示其至少部分作用可能继发于其钙动员作用。
Earlier observations that arachidonic acid inhibited the synthesis of membrane inositol phospholipids in rat submandibular acinar cells prompted the present study on whether the fatty acid may also regulate other key physiological processes in the model. Arachidonate, at concentrations above 10 mu mol/L, inhibited up to 97% protein synthesis in acinar cells. The acid also lowered cellular ATP levels to 25% of control values by a ouabain-insensitive mechanism. In endoplasmic reticulum-calcium studies in permeabilized cells, arachidonic acid stimulated the mobilization of up to 73% loaded ER-Ca-45(2+) to the cytosol, a much greater response than those caused by other calcium translocators, thapsigargin or inositol 1,4,5-trisphosphate. Additionally, arachidonate provoked the release of over 80% of total cell Ca-45(2+) to the extracellular space in intact cells and stimulated mucin secretion in the submandibular model. The inhibitory effect of arachidonic acid on protein synthesis was duplicated by carbachol, thapsigargin, and BAPTA/AM, three agents that cause net efflux of ER-Ca2+ by different mechanisms. Furthermore, comparable with the arachidonate effect on ATP, carbachol and thapsigargin also significantly reduced cellular levels of the nucleotide. It is concluded that arachidonic acid acts as a regulator of central synthetic/secretory processes in mucous acinar cells of rat submandibular gland and suggested that at least some of its effects may be secondary to its calcium-mobilizing action.