1996 Fiscal Year Final Research Report Summary
Physiological Signiticance of Phospholipase A_2 activation in neuronal activity.
| Project/Area Number |
07660407
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Basic veterinary science/Basic zootechnical science
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| Research Institution | Osaka Pretecture University |
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Principal Investigator |
TAKEUCHI Tadayoshi Osaka Prefecture University, Agriculture, Assistant Professor, 農学部, 助教授 (00171611)
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| Project Period (FY) |
1995 – 1996
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| Keywords | Phospholipase A_2 / Acetylcholine Release / Ca^<2+>-independent fusion / Guinea Pig Myenteric Plexus / Rat Brain Synaptosome / Auto, inhibition / Protein Kinase C / Arachidonate Metabolism |
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| Research Abstract |
The results obtained from this study are as follows ; an activation of protein kinase A is essential for modulation of the agonist-induced release of acetylcholine (Ach) from myenteric plexus of guinea pig ileum, and the activity of protein kinase A is regulated by prostaglandins, which was synthesized from arachidonic acid released by phospholipase A_2(PLA_2), via intracellular cyclic AMP level in myenteric neurons. In addition, an inhibition of Ach release by activation of muscarnic autoreceptor on presynaptic membranes is attributed in part to an depression of phospholipase C-protein kinase C system. The Ach releases induced by electrical field stimulation in the presence of atropine (under the autoinhibition-blocked condition) or by an activation of protein kinase C were inhibited significantly by an inhibitor of PLA_2, suggesting that protein kinase C may regulate the activity of PLA_2. These results indicate that the activity of PLA_2 and metabolites of arachidonic acid are impor
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tant factors in neurotransmitter-releasing mechanisms, and the regulation of Ach release with physiological active substances may be due to an action on its enzyme.
In another experiment, synaptic vesicle and presynaptic membrane were prepared from rat brain. Synaptic vesicle fused with presynaptic membrane which had been pretreated with PLA_2 in the presence of Ca^<2+> and released Ach, whereas synaptic vesicles did not interact with non-pretreated membrane. However, Ca^<2+> were not required for the fusion itself. Arachidonic acid potentiated the fusogenic activity of membrane. In rat parotid acinar cells as endocrine tissue, the activation of PLA_2 was involved in a fusion of and a release of amylase from the secretary ranules with plasma membrane. These finding suggest that PLA_2 activity is important in the process of fusion in the regulated exocytosis.
In conclusion, it was clear that PLA_2 has a pivotal role for regulating the exocytosis involving neurotransmitter release and enzyme secretion. Less
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