This proposal is designed to study chromogranin A, the quantitatively major soluble protein in mammalian catecholamine storage vesicles. It is costored and coreleased with catecholamines from vesicles in the adrenal medulla and noradrenergic nerves, and has been used as an index of exocytotic catecholamine release in isolated, perfused organs. This proposal will evaluate and measure chromogranin A (CgA) in intact organisms, especially man, in order to evaluate its usefulness as an index of sympathoadrenal activity, with the goal of applying it to human disease states, such as hypertension, where sympathetic activity may be disordered. CgA has been purified, in our laboratory, from catecholamine storage vesicles of man (pheochromocytoma), cow (adrenal medulla), and rat (adrenal medulla). I will continue the characterization of these molecules. Our laboratory has developed a radioimmunoassay for bovine CgA, and I will apply a human CgA radioimmunoassay to human studies, looking at plasma CgA in plasma of normotensive and hypertensive man, under basal states as well as states of sympathoadrenal activation and suppression, to see whether its level parallels the state of sympathetic nervous system activity. We feel the research is important, because it may lead to a new and perhaps improved way of evaluating the sympathetic nervous system in human disease, particularly hypertension.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Physician Scientist Award (K11)
Project #
5K11HL001416-04
Application #
3087175
Study Section
Research Manpower Review Committee (MR)
Project Start
1984-07-01
Project End
1989-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
4
Fiscal Year
1987
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
Parmer, R J; Cervenka, J H; Stone, R A (1992) Baroreflex sensitivity and heredity in essential hypertension. Circulation 85:497-503
Parmer, R J; Cervenka, J H; Stone, R A et al. (1990) Autonomic function in hypertension. Are there racial differences? Circulation 81:1305-11
Parmer, R J; Koop, A H; Handa, M T et al. (1989) Molecular cloning of chromogranin A from rat pheochromocytoma cells. Hypertension 14:435-44
Parmer, R J; O'Connor, D T (1988) Enkephalins in human phaeochromocytomas: localization in immunoreactive, high molecular weight form to the soluble core of chromaffin granules. J Hypertens 6:187-98
Parmer, R J; Mosley, C; O'Connor, D T (1985) Enkephalins in pheochromocytoma: studies in a rat model. Clin Exp Hypertens A 7:483-512