O'Connor D T
Regul Pept. 1983 Jul;6(3):263-80. doi: 10.1016/0167-0115(83)90145-3.
Chromogranin A is the major soluble protein, co-stored and co-released with catecholamines from storage vesicles of adrenal medulla and sympathetic nerve, and has been used as an index of exocytotic sympathoadrenal neurosecretion. Since some neuropeptides have a rather wide distribution in nerve, gut, and endocrine glands, we used a sensitive chromogranin A radioimmunoassay to probe the occurrence of chromogranin in several polypeptide hormone producing tissues. Immunoreactive chromogranin was ubiquitous in such tissues, in rank order of concentration (microgram/g wet weight): adrenal medulla greater than pituitary gland (anterior greater than intermediate greater than posterior) greater than pancreas greater than small intestine greater than thyroid greater than hypothalamus. In each case, the tissue homogenate displaced 125I-labelled chromogranin A from antibody in parallel with displacement generated by pure unlabeled chromogranin A, and the immunoreactivity was not abolished by boiling or by several protease inhibitors. Quantitatively, the endocrine tissues other than adrenal medulla possessed 0.1-2.8% of the immunoreactivity found in the adrenal medulla. Immunoreactive chromogranin was also present in serum and sympathetic nerve, but contamination of the endocrine tissues by chromogranin from serum or sympathetic innervation could not account for the observed immunoreactivity. Immunoreactive chromogranin was undetectable in platelets. Tissues with predominant exocrine function (salivary glands) had very little chromogranin (0.004-0.005% of that found in the adrenal medulla). Within the cell, differential centrifugation localized the immunoreactive chromogranin to a hormone storage granule fraction in the anterior pituitary gland (60 +/- 6% of total, with 2.0 +/- 0.3-fold enrichment in the granule) and the adrenal medulla (74 +/- 13% of total, with 1.7 +/- 0.2-fold enrichment in granules). Gel filtration suggested a lower effective molecular radius for pituitary and pancreatic immunoreactive chromogranin than for purified 125I-labelled chromogranin A. Thus, chromogranin in the other endocrine glands differed from adrenal medullary chromogranin both quantitatively (less microgram/g tissue) and qualitatively (lower molecular weight). The results suggest a widespread, though as yet undefined, role for chromogranin in the neurosecretory process, and raise the possibility that chromogranin may be co-stored and secreted with a variety of polypeptide hormones.
嗜铬粒蛋白A是主要的可溶性蛋白，与儿茶酚胺共同储存并从肾上腺髓质和交感神经的储存囊泡中共同释放，并且已被用作胞吐性交感肾上腺神经分泌的指标。由于一些神经肽在神经、肠道和内分泌腺中分布相当广泛，我们使用灵敏的嗜铬粒蛋白A放射免疫分析法来探究嗜铬粒蛋白在几种产生多肽激素的组织中的存在情况。免疫反应性嗜铬粒蛋白在这些组织中普遍存在，按浓度（微克/克湿重）排序为：肾上腺髓质＞垂体（前叶＞中间叶＞后叶）＞胰腺＞小肠＞甲状腺＞下丘脑。在每种情况下，组织匀浆与纯未标记的嗜铬粒蛋白A产生的置换作用平行，从抗体中置换出125I标记的嗜铬粒蛋白A，并且免疫反应性不会因煮沸或几种蛋白酶抑制剂而消除。定量分析表明，除肾上腺髓质外的内分泌组织的免疫反应性为肾上腺髓质的0.1 - 2.8%。免疫反应性嗜铬粒蛋白也存在于血清和交感神经中，但血清或交感神经支配的嗜铬粒蛋白对内分泌组织的污染不能解释所观察到的免疫反应性。血小板中未检测到免疫反应性嗜铬粒蛋白。具有主要外分泌功能的组织（唾液腺）中嗜铬粒蛋白含量极少（为肾上腺髓质中含量的0.004 - 0.005%）。在细胞内，差速离心将免疫反应性嗜铬粒蛋白定位于垂体前叶的激素储存颗粒部分（占总量的60±6%，在颗粒中富集2.0±0.3倍）和肾上腺髓质（占总量的74±13%，在颗粒中富集1.7±0.2倍）。凝胶过滤表明，垂体和胰腺的免疫反应性嗜铬粒蛋白的有效分子半径低于纯化的125I标记的嗜铬粒蛋白A。因此，其他内分泌腺中的嗜铬粒蛋白在数量上（每克组织中微克数较少）和质量上（分子量较低）均与肾上腺髓质嗜铬粒蛋白不同。结果表明嗜铬粒蛋白在神经分泌过程中具有广泛但尚未明确的作用，并增加了嗜铬粒蛋白可能与多种多肽激素共同储存和分泌的可能性。
