Chromogranin A (CgA) is the major soluble protein stored in catecholamine storage vesicles in the adrenal medulla and sympathetic nerves. Its plasma concentration varies as a function of sympathoadrenal activation. Circulating plasma CgA is modestly elevated in essential hypertension, suggesting an excess of exocytotic sympathoadrenal activity in this disorder. However, whether adrenergic tissue CgA synthesis and storage, processes potentially underlying this rise in plasma CgA, are altered in hypertension is unknown. In addition, knowledge of its intracellular processing and secretion is incomplete. In particular, whether CgA is secreted unaltered by exocytosis from storage vesicles, and how it is intracellulary processed is unknown. This proposal involves the use of synthetic peptides, corresponding to different domains of the CgA molecule, and their corresponding polyclonal antisera. This allows us to study intracellular processing of CgA in isolated chromaffin cells, and as well as to examine adrenergic tissue CgA synthesis and storage in rat experimental hypertension models. Hence, the physiologic significance of the rise in plasma CgA and alterations in exocytotic sympathoadrenal activity in human hypertension will be better elucidated.
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