Abstract

This study examines the neuronal response to neuromodulators that interact with the adenylate cyclase system of the cell. Neuroblastoma cells in culture have been shown to respond to Alpha-adrenergic and muscarinic agents by a decreased synthesis of cyclic AMP. The mechanism of the adenylate cyclase inhibition in this and other cell types has not been fully elucidated. Other systems, muscarinic and Alpha-adrenergic hormones alter cell membrane phospholipids in such a way as to promote Ca++ mobilization and arachidonic acid release as intermediary functions mediating the tissue specific response. Recent findings in my laboratory are consistent with a mechanism of phospholipid metabolism as a concurrent response to the inhibition of adenylate cyclase in neuroblastoma cells. It is the purpose of the proposed studies to examine the relationship between adenylate cyclase inhibition and the membrane phospholipid events leading to arachidonic acid release and metabolism in neuroblastoma cells. It is expected that these experiments will advance our understanding of neurotransmitter and hormone actions in the nervous system.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS016513-05
Application #
3396935
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1980-09-30
Project End
1987-02-28
Budget Start
1985-03-01
Budget End
1986-02-28
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Saint Louis University
Department
Type
Schools of Medicine
DUNS #
City
Saint Louis
State
MO
Country
United States
Zip Code
63103

  Publications

O'Donnell, K A; Howlett, A C (1991) Inhibition of adenylate cyclase by p-bromophenacyl bromide. Biochem Pharmacol 42:1941-6
O'Donnell, K A; Howlett, A C (1991) Muscarinic receptor binding is inhibited by quinacrine. Neurosci Lett 127:46-8
Howlett, A C; Scott, D K; Wilken, G H (1989) Regulation of adenylate cyclase by cannabinoid drugs. Insights based on thermodynamic studies. Biochem Pharmacol 38:3297-304
Anschutz, A; Howlet, A; Klein, C (1989) GDP stimulates the phosphorylation of a 36-kDa membrane protein in Dictyostelium discoideum. Proc Natl Acad Sci U S A 86:3665-8
Beinfeld, M C; Brick, P L; Howlett, A C et al. (1988) The regulation of vasoactive intestinal peptide synthesis in neuroblastoma and chromaffin cells. Ann N Y Acad Sci 527:68-76
Khachatrian, L; Klein, C; Howlett, A (1987) Pertussis and cholera toxin ADP-ribosylation in Dictyostelium discoideum membranes. Biochem Biophys Res Commun 149:975-81
Khachatrian, L; Howlett, A; Klein, C (1987) Ammonium sulfate modifies adenylate cyclase and the chemotactic receptor of Dictyostelium discoideum. Evidence for a G protein effect. J Biol Chem 262:8071-6
Khachatrian, L; Klein, C; Howlett, A (1987) Regulation of Dictyostelium discoideum adenylate cyclase by manganese and adenosine analogs. Biochim Biophys Acta 927:235-46
Walz, M A; Howlett, A C (1987) Thyroid effects on adenosine 3',5'-monophosphate levels and adenylate cyclase in cultured neuroblastoma cells. Endocrinology 120:1265-71
Watz, M A; Holt, I L; Howlett, A C (1987) Cyclic nucleotide phosphodiesterase isozymes in neuroblastoma cells. J Neurosci Res 17:291-7

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