| Project/Area Number |
10672150
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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 |
応用薬理学・医療系薬学
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| Research Institution | The University of Tokushima |
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Principal Investigator |
MINAKUCHI Kazuo The University of Tokushima, Pharmacy, Professor, 医学部・附属病院, 教授 (30284326)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIZUMI Masanori The University of Tokushima, Pharmacology, Assistant, 医学部, 助手 (60294667)
SHIMIZU Eiji The University of Tokushima, Third Internal Medicine, Assistant Professor, 医学部, 講師 (50187449)
HOUCHI Hitoshi The University of Tokushima, Pharmacy, Associate Professor, 医学部・附属病院, 助教授 (00219156)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1999: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1998: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Keywords | Adrenal Chromaffin Cells / Neuronal Cells / Calcium Efflux / Anti-hypertensive Drugs |
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| Research Abstract |
In adrenal chromaffin cells, which are regarded as model catecholamine-containing neurons and are useful for studies on the mechanism of stimulus-secretion coupling, secretory stimulation causes an increase in the intracellular free CaィイD12+ィエD1 ([CaィイD12+ィエD1]i) level originating from intracellular pools and extracellular spaces, leading to catecholamine secretion and activation of catecholamine biosynthesis. After stimulation, the increased [CaィイD12+ィエD1]i should rapidly return to the resting level for response to a subsequent stimulation. Opiate peptides such as enkephalins are thought to be stored in the secretory vesicles in the cells, and are co-secreted with catecholamines in response to decreasing the elevated [CaィイD12+ィエD1]i in adrenal chromaffin cells after physiological stimulation. In this study, we investigated the mechanism of this decrease in elevated [CaィイD12+ィエD1]i and examined the effects of enkephalins on CaィイD12+ィエD1 efflux from bovine adrenal chromaffin cells in culture.
The effects of leucine- and methionine-enkephalin, opiate peptides, on CaィイD12+ィエD1 efflux from cultured bovine adrenal chromaffin cells were examined. These enkephalins stimulated the efflux of ィイD145ィエD1CaィイD12+ィエD1 from cells in a concentration-dependent manner (10ィイD1-8ィエD1M - 10ィイD1-6ィエD1M). Leucine-enkephalin did not increase the [CaィイD12+ィエD1]i, ィイD145ィエD1CaィイD12+ィエD1 uptake, catecholamine secretion, CAMP Level or cGMP Level. The peptide-stimulated ィイD145ィエD1CaィイD12+ィエD1 efflux was not inhibited by incubation in CaィイD12+ィエD1-free medium, but was inhibited by incubation in NaィイD1+ィエD1-free medium. These results indicate that enkephalins stimulate extracellular NaィイD1+ィエD1-dependent ィイD145ィエD1CaィイD12+ィエD1 efflux from cultured bovine adrenal chromaffin cells, probably by stimulating membrane NaィイD1+ィエD1/CaィイD12+ィエD1 exchange. Thus, new compounds which have the stimulatory effects of CaィイD12+ィエD1 efflux may indicate anti-hypertensive effects.
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