The purpose of this research is to elucidate the mechanisms that regulate adrenal catecholamine synthesis and secretion. Catecholamine synthesis and secretion will be studied in suspensions of pheochromocytoma cells and of normal chromaffin cells. I have recently developed a method for the on-line monitoring of catecholamine secretion from superfused chromaffin cells. With this method, I will study the kinetics of catecholamine secretion and the desensitization and recovery of the secretory response to acetylcholine and to other stimuli. I have also developed a method for measuring the activity of tyrosine 3-monooxygenase (tgyrosine hydroxylase) in intact chromaffin cells. In this method, cells are incubated with tyrosine, and the rate of production of dihydroxyphenylalanine is measured by liquid chromatography with electrochemical detection. I will use this method to study the co-ordinate regulation of catecholamine secretion and of tyrosine hydroxylase activity. In particular, I will examine the roles of cyclic adenosine 3':5'-monophosphate and of Ca++ in these processes. I will also study the effects of ionophores, such as lasalocid and monesin, on these processes. Finally, I will investigate the role of adenosine in the regulation of adenylate cyclase activity and tyrosine hydroxylase activity in chromaffin cells.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL029025-05
Application #
3340207
Study Section
Endocrinology Study Section (END)
Project Start
1981-09-01
Project End
1986-04-30
Budget Start
1985-05-01
Budget End
1986-04-30
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Illinois at Chicago
Department
Type
Overall Medical
DUNS #
121911077
City
Chicago
State
IL
Country
United States
Zip Code
60612
Cahill, A L; Perlman, R L (1994) Tetraethylammonium selectively stimulates secretion from noradrenergic bovine chromaffin cells. J Auton Pharmacol 14:177-85
Tischler, A S; Freund, R; Carroll, J et al. (1993) Polyoma-induced neoplasms of the mouse adrenal medulla. Characterization of the tumors and establishment of cell lines. Lab Invest 68:541-9
Choi, A Y; Cahill, A L; Perry, B D et al. (1993) Histamine evokes greater increases in phosphatidylinositol metabolism and catecholamine secretion in epinephrine-containing than in norepinephrine-containing chromaffin cells. J Neurochem 61:541-9
Pavlovic-Surjancev, B; Cahill, A L; Perlman, R L (1993) Staurosporine activates a 60,000 M(r) protein kinase in bovine chromaffin cells that phosphorylates myelin basic protein in vitro. J Neurochem 61:697-703
Cahill, A L; Perlman, R L (1992) Phorbol esters cause preferential secretion of norepinephrine from bovine chromaffin cells. J Neurochem 58:768-71
Pavlovic-Surjancev, B; Cahill, A L; Perlman, R L (1992) Nicotinic agonists, phorbol esters, and growth factors activate two extracellular signal-regulated kinases, ERK1 and ERK2, in bovine chromaffin cells. J Neurochem 59:2134-40
Cahill, A L; Perlman, R L (1991) Phosphotyrosine-containing proteins in bovine chromaffin cells: effects of insulin-like growth factor I (IGF-I). Cell Mol Neurobiol 11:387-95
Cahill, A L; Perlman, R L (1991) Activation of a microtubule-associated protein-2 kinase by insulin-like growth factor-I in bovine chromaffin cells. J Neurochem 57:1832-9
Tischler, A S; Ruzicka, L A; Perlman, R L (1990) Mimicry and inhibition of nerve growth factor effects: interactions of staurosporine, forskolin, and K252a in PC12 cells and normal rat chromaffin cells in vitro. J Neurochem 55:1159-65
Dahmer, M K; Hart, P M; Perlman, R L (1990) Studies on the effect of insulin-like growth factor-I on catecholamine secretion from chromaffin cells. J Neurochem 54:931-6

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