O'Connor D T, Frigon R P
J Biol Chem. 1984 Mar 10;259(5):3237-47.
Chromogranin A (CgA), the major catecholamine storage vesicle (CSV) soluble protein, may index exocytotic sympathoadrenal secretion. To explore CgA in adrenergic tissues, we developed a radioimmunoassay for bovine CgA. Within adrenal medulla CSV, several minor chromogranins had similar amino acid compositions and peptide maps to that of CgA and also showed parallel, partial cross-reactivity in the CgA radioimmunoassay. CgA immunoreactivity represented 7 +/- 1% of total adrenal medulla cell protein and was localized to adrenal CSV, representing 46 +/- 2% of CSV soluble protein. In brain, there was 1000-fold less CgA than in adrenal medulla, with a widespread regional distribution (maximal in neocortex) and an unusual subcellular distribution (maximal in cytosol), both of which differ from reported catecholamine distribution. Brain chromogranin immunoreactivity also had a lower Stokes radius than adrenal CgA. Sympathetic nerve and serum had 6,000-fold and 30,000-fold less CgA than that in adrenal medulla. The results suggest a "family" of adrenal medulla chromogranins, similar structurally and immunoligically. Adrenal medulla and brain chromogranin differ in concentration, subcellular localization, and molecular size. Finally, CgA in serum may provide a useful tool for sympathoadrenal studies in intact organisms.
嗜铬粒蛋白A(CgA)是主要的儿茶酚胺储存囊泡(CSV)可溶性蛋白,可能是胞吐性交感肾上腺分泌的指标。为了研究肾上腺能组织中的CgA,我们开发了一种针对牛CgA的放射免疫分析法。在肾上腺髓质CSV中,几种次要的嗜铬粒蛋白具有与CgA相似的氨基酸组成和肽图,并且在CgA放射免疫分析法中也显示出平行的部分交叉反应性。CgA免疫反应性占肾上腺髓质细胞总蛋白的7±1%,定位于肾上腺CSV,占CSV可溶性蛋白的46±2%。在脑中,CgA比肾上腺髓质中的含量少1000倍,具有广泛的区域分布(在新皮质中最高)和不寻常的亚细胞分布(在胞质溶胶中最高),这两者都与报道的儿茶酚胺分布不同。脑嗜铬粒蛋白免疫反应性的斯托克斯半径也比肾上腺CgA小。交感神经和血清中的CgA比肾上腺髓质中的分别少6000倍和30000倍。结果表明肾上腺髓质嗜铬粒蛋白存在一个“家族”,在结构和免疫方面相似。肾上腺髓质和脑嗜铬粒蛋白在浓度、亚细胞定位和分子大小方面存在差异。最后,血清中的CgA可能为完整生物体中的交感肾上腺研究提供一个有用的工具。