Waschek J A, Dave J R, Eskay R L, Eiden L E
Biochem Biophys Res Commun. 1987 Jul 31;146(2):495-501. doi: 10.1016/0006-291x(87)90556-0.
The effect of barium and potassium on the secretion and biosynthesis of enkephalin in bovine chromaffin cells, and prolactin and beta-endorphin in rat anterior pituitary cells, was examined to determine whether calcium-dependent secretion and biosynthesis are mediated by the same or by different calcium targets within the neuroendocrine cell. In the presence of 1.8 mM calcium, barium and potassium stimulated the secretion of all three peptides over 30 min, and increased the levels of proenkephalin and prolactin mRNA in 24 hr. These effects were inhibited by the calcium channel blocker D600. When the extracellular calcium concentration was lowered to 0.1 mM or less, secretion elicited by potassium was blocked, whereas secretion elicited by barium was enhanced, indicating that barium wholly substitutes for extracellular calcium in mediating peptide secretion. On the other hand, stimulation of proenkephalin and prolactin mRNA by both potassium and barium was inhibited when the extracellular calcium concentration was reduced. We conclude that calcium acts at two different intracellular targets to activate secretion versus biosynthesis of both enkephalin and prolactin. This appears to be the first report in which two different calcium-dependent processes in the intact cell are distinguished by a calcium ion agonist. Calcium-dependent processes such as protein phosphorylation, protein translocation, and enzyme activation may thus be related to events in the intact cell such as peptide synthesis and secretion on the basis of selective stimulation by barium.
研究了钡和钾对牛嗜铬细胞中脑啡肽分泌及生物合成，以及对大鼠垂体前叶细胞中催乳素和β-内啡肽分泌及生物合成的影响，以确定神经内分泌细胞内钙依赖性分泌和生物合成是由相同的钙靶点还是不同的钙靶点介导的。在存在1.8 mM钙的情况下，钡和钾在30分钟内刺激了所有三种肽的分泌，并在24小时内增加了前脑啡肽和催乳素mRNA的水平。这些作用被钙通道阻滞剂D600抑制。当细胞外钙浓度降低到0.1 mM或更低时，钾引发的分泌被阻断，而钡引发的分泌增强，这表明钡在介导肽分泌方面完全替代了细胞外钙。另一方面，当细胞外钙浓度降低时，钾和钡对前脑啡肽和催乳素mRNA的刺激均被抑制。我们得出结论，钙作用于两个不同的细胞内靶点，以激活脑啡肽和催乳素的分泌与生物合成。这似乎是第一份用钙离子激动剂区分完整细胞中两种不同钙依赖性过程的报告。因此，基于钡的选择性刺激，蛋白质磷酸化、蛋白质转运和酶激活等钙依赖性过程可能与完整细胞中的肽合成和分泌等事件相关。
