Chromogranin A is the major soluble protein stored and secreted by exocytosis, along with catecholamines, from vesicles in the adrenal medulla and sympathetic nerves. We investigated the possible use of chromogranin A as a probe of exocytotic sympathoadrenal activity, by developing a radioimmunoassay for chromogranin A purified from pheochromocytoma vesicles. In 18 normal recumbent men chromogranin A was present in plasma at a concentration of 129 +/- 12 ng per milliliter. The concentration varied with physiologic, pharmacologic, and pathologic changes in sympathoadrenal activity. It rose with standing and fell with recumbency, though it was not perturbed by brief dynamic exercise. It rose during brief vasodilation and fell during stimulation of nonexocytotic catecholamine release by tyramine and during ganglionic blockade. The plasma concentration of chromogranin A was elevated in 11 patients with pheochromocytoma (1614 +/- 408 ng per milliliter). The mean plasma half-life was 18.4 minutes. We conclude that both resting and activated sympathoadrenal tone in normal persons, as well as catecholamine secretion by pheochromocytoma, are at least in part exocytotic in mechanism and that chromogranin A may be a useful probe of exocytotic sympathoadrenal activity.
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