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 inhibiton in this and other cell types has not been fully elucidated. In 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.
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