ENZYMATIC AUTOMODULATION OF CHEMICAL PRESYNAPTIC NEUROTRANSMISSION.
Item
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Title
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ENZYMATIC AUTOMODULATION OF CHEMICAL PRESYNAPTIC NEUROTRANSMISSION.
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Identifier
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AAI8319785
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identifier
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8319785
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Creator
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MOSKOWITZ, NATHAN.
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Contributor
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Saul Puszkin
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Date
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1983
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biophysics, Medical
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Abstract
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A variety of enzymes in brain synaptic and coated vesticles and presynaptic plasma membrane were characterized. It was found that synaptic and coated vesicles and synaptic plasma membrane had endogenous calcium-dependent phospholipase A(,2) (PLA(,2)). In all three membrane preparations, calmodulin and prostaglandin F(,2(alpha)) (PGF(,2(alpha))) stimulated whereas ATP inhibited both synaptic vesicle and synaptic plasma membrane PLA(,2) activities, whereas it stimulated coated vesicle PLA(,2) activity. Cyclic-AMP by itself inhibited coated vesicle and synaptic plasma membrane PLA(,2) activities, whereas it stimulated synaptic vesicle activity. Furthermore, conditions which were conducive to stimulation of cAMP dependent protein kinase in synaptic vesicles also stimulated synaptic vesicle PLA(,2) activity. The modulation of PLA(,2) activities in the three membrane preparations studied were correlated with function via light scattering, light microscopic and electron microscopic techniques. Conditions in general which stimulated endogenous membrane PLA(,2) activity induced vesicle aggregation and membrane distortion, conditions conducive to both exocytosis and endocytosis. Based on enzymatic and protein cross-linking studies it was found that a variety of purified soluble PLAs(,2) were modulated by calmodulin, PGF(,2(alpha)), cAMP and cGMP. On the basis of this data a scheme for PLA(,2) polymerization pathways was postulated. Synaptic and coated vesicles also were found to have endogenous calcium/calmodulin-dependent protein kinase, {lcub}Ca('2+)-Mg('2+){rcub}-ATPase and PGF synthetase activities. Synaptic vesicles in addition were found to have endogenous cAMP-dependent protein kinase activity. This thesis presents a unified theory of presynaptic neurotransmission which invokes a series of parallel and interconnecting enzymatic cascades which operate simultaneously and synergistically to modulate presynaptic chemical neurotransmission.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
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Program
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Biomedical Sciences
