| Budget Amount *help |
¥16,100,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2007: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2006: ¥8,300,000 (Direct Cost: ¥8,300,000)
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| Research Abstract |
We have proposed that L-3,4-dihydroxyphenylalanine (DOPA), the precursor of dopamine, is a neurotransmitter in the central nervous system. However its specific receptor(s) have not been determined yet. In this proposal, we have tried to identify specific ligands for DOPA recognistion site(s), namely DOPAreceptor(s), and investigate structure-activity relationship by using blood-pressure monitoring system in anaesthetized rats. DOPA or L-threo-DOPS, a precursor of noradrenaline, when microinjected into the nucleus tractus solitarii (NTS), induces depressor and baradycardic responses. By using HPLC, we found an active fraction of DOPA or DOPS-containing solution other than that of DOPA and DOPS itself that induced depressor and bradycardic responses. We obtained A113 and S122 fractions from DOPA and DOPS-containing solutions, respectively, both of which were active in inducing the cardiovascular responses in anaesthetized rats. In addition, these responses were antagonized by L-DOPA cycl
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ohexylester (DOPA CHE), an competitive antagonist for DOPA, thereby suggesting that some unknown active substances in DOPA and DOPS solution induced depressor and bradycardic responses through the recognition site(s) for DOPA. We are now trying further purification, identification and structural determination of these substances.
The second project aimed at identification and characterization of a DOPA receptor candidate gene, C06H5.7 in C elegans. Using Xenopus laevis oocyte expression system, we identified a candidate G-protein-coupled receptor, that mediates current response to DOPA C06H5.7 was expressed in ASH chemosensory neurons. In C06H5.7 mutant animals, the avoidance response to undiluted benzaldehyde, but not to 1-octanol, was attenuated. C06H5.7, when exogenously expressed in ASH neurons, rescued the responsiveness to benzaldehyde. Furthermore, we found some water-soluble substance as a novel repellent acting on this receptor in C elegans. These results indicate that C06H5.7 is not a receptor for DOPA but the first chemosensory receptor that mediates aversive response to volatile and water soluble chemorepellents. Less
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