Chromogranin: widespread immunoreactivity in polypeptide hormone producing tissues and in serum

Abstract

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.