2005 Fiscal Year Final Research Report Summary
Functional analysis of novel G-coupled receptor candidate for L-DOPA and structural determination of its ligands
| Project/Area Number |
16390068
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Yokohama City University Graduate School of Medicine |
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Principal Investigator |
GOSHIMA Yoshio Yokohama City University, Molecular Pharmacology, Professor, 大学院・医学研究科, 教授 (00153750)
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| Co-Investigator(Kenkyū-buntansha) |
YAGAMI Tatsuro Yokohama City University, Molecular Pharmacology, Research Associate, 医学部(現姫路獨協大学), 助手(教授) (00363812)
NAKAMURA Fumio Yokohama City University, Molecular Pharmacology, Assistant Professor, 医学部, 準教授 (10262023)
KAJIWARA Yasuhiro Yokohama City University, Molecular Pharmacology, Assistant Professor, 大学院・国際総合科学研究科, 準教授 (50275020)
KAMIYA Yoshitaka Yokohama City University, Molecular Pharmacology, Research Associate, 附属病院, 助手 (90381491)
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| Project Period (FY) |
2004 – 2005
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| Keywords | DOPA / Benzaldehyde / Caenorhabditis elegans / chemotaxis / blood pressure control / monoamine receptors |
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| Research Abstract |
We proposed L-3,4-dihydroxyphenylalanine (DOPA) as a neurotransmitter candidate of baroreceptor afferent neurons terminating in the nucleus tractus solitarii (NTS). We have isolated C.elegans C06H5.7 gene as a receptor candidate for DOPA through expression screening using Xenopus laevisoocytes. Electrophysiological analyses of C06H5.7 showed that C06H5.7 responded to non-amine metabolites of DOPA, but did not to itself. Previously, we have reported that 3,4-dihydroxybenzaldehyde (DHBALD) acts as one of active ligands for C06H5.7. An odorant benzaldehyde that is similar to DHBALD in the chemical structure electrophysiologically activated C06H5.7. Although benzaldehyde at low concentrations sensed by AWC sensory neurons is a chemoattractants in C.eleagans, expression of C06H5.7 have not yet been detected in AWC. A null mutant candidate for C06H5.7, nj66,was not defective in the attraction by benzaldehyde. On the other hand, benzaldehyde at high concentrations sensed by ASH sensory neurons is a chemorepellent in C.eleagans, but its receptor has not yet been identified. To test the possibility that C06H5.7 is involved in the aversive mechanisms, we are performing the aversion assay of nj66 and detecting the expression of C06H5.7 in the ASH. However, these ligands produced no effects on blood pressure and hear rates of anesthetized rats, when these were microinjected into the nucleus tractus solitarii.
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