| Project/Area Number |
11680770
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | Department of Pharmacology, Nagasaki University School of Medicine (2000)
宮崎医科大学 (1999) |
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Principal Investigator |
UEZONO Yasuhito Nagasaki university School of Medicine, Assistant Professor, 医学部, 講師 (20213340)
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| Co-Investigator(Kenkyū-buntansha) |
SHIBUYA Izumi University of Occupational and Environmental Health, School of Medicine, Associate Professor, 医学部, 助教授 (50162649)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1999: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | GABA-B receptors / G-protein coupled receptors / heteromultimerization / inwardly rectifying K+ channels / Xenopus oocytes / heterologous expression / adrenomedullin / calcitonin gene-related peptide / GABA-B受容体 / heterodimerization / Xenopus oocyte / CFTR / Electrophysiology |
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| Research Abstract |
γ-Amino butyric acids (GABA) is known to act as an inhibitory neurotransmitter on the central and peripheral nervous system. Receptors for GABA are divided into two types : one belongs to ionotropic receptors (GABA_A and GABA_C) and another belongs to metabotoropic G-protein coupled receptors (GABA_B). GABA_B receptor has been cloned in 1997 as a GABA_<B1> receptor and since then, a lot of works have been focused on the heterologous functional expression of the cloned GABA_B receptors. However, none of the expression study has succeeded. Accodingly the failure of the expression study suggested us the existence of some additional protein (s) for the functional expression of GABA_B receptors. We have previously reported that functional GABA_B receptors are actually expressed in Xenopus oocytes expressing the rat brain poly(A)^+ RNA which abundantly express the GABA_B receptor (Uezono et al., Biochem. Biophys. Res. Commun. 241 : 476- (1997) ; Uezono et al., NeuroReport 9 : 583- (1998)). W
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e therefore determined to clone the 'GABA_B receptor expressing factor (s)' with the oocytes expressing both the rat poly(A)^+ RNA and cloned GABA_<B1> receptor.
In the course of such experiments, others have demonstrated in late 1998 that heteromultimerization of GABA_<B1> and newly cloned GABA_<B2> receptors are required for functional expression of GABA_B receptors.
So we have changed our mind to investigate the mechanism of how GABA_B receptors are required heteromultimerization to be functional, with the cloned GABA_<B2> and GABA_<B2> receptors. In the mean time, another type of metabotoropic receptor namely adrenomedullin receptor is found to form complex with calcitonin receptor-like receptor (CRLR) and small proteins called 'receptor-activity-modifying proteins (RAMPs)' to be functional. We then took advantage of adrenomedullin receptors (CRLR and RAMPs) and compared the mechanism of adrenomedullin receptor formation with that of GABA_B receptor formation.
We are still in progress of our study and hope to continue to clarify the mechanism how GABA_B receptors are formed and why GABA_B receptors are required to be heteromultimer for their functional expression Less
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