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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29HL043275-03
Application #
3472779
Study Section
Endocrinology Study Section (END)
Project Start
1989-07-01
Project End
1994-06-30
Budget Start
1991-07-01
Budget End
1992-06-30
Support Year
3
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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