2002 Fiscal Year Final Research Report Summary
Analysis of the molecular mechanisms of formation and trafficking to the cell surface of the G protein-coupled receptors that require accessory proteins for their expression.
| Project/Area Number |
13680846
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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 | Nagasaki University Graduate School of Biomedical Sciences |
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Principal Investigator |
UEZONO Yasuhito Nagasaki Univ. Grad. Sch. Biomed. Sci. Assistant Professor, 大学院・医歯薬学総合研究科, 講師 (20213340)
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| Co-Investigator(Kenkyū-buntansha) |
TANIYAMA Kohtaro Nagasaki Univ. Grad. Sch. Biomed. Sci, Professor, 大学院・医歯薬学総合研究科, 教授 (70030898)
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| Project Period (FY) |
2001 – 2002
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| Keywords | GABA_B receptors / G-protein coupled receptors / Heteromultimerization / Xenopus oocytes / Heterologous expression / FRET / Electrophysiology / Laser confocal microscopy |
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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, many of works have been focused on the heterologous functional expression of the cloned GABA_B receptors. However, none of the expression study has succeeded. Accordingly the failure of the expression study suggested us the existence of some additional protein(s) for the functional expression of GABA_B receptors. Now functional GABA_B receptors are known to be required to be formed heterodimer with GABA_<B1> and GBA_<B2> receptors.
In the present study we focused on how functional GABA_B receptors are constructed as heterodimer and how the receptors are trafficked to the cell membrane, by the use of multiple assay systems. We found that functional GABA_B receptors are already formed before trafficked to cell membranes. We also found that GABA_<B1> receptors are required for their ligand binding while GABA_<B2> receptors are indispensable for their intracellular signaling through heteromeric G proteins.
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.
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Research Products
(32 results)
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[Publications] SHIRAISHI, S., SHIBUYA, I., UEZONO, Y., YOKOO, H., TOYOHIRA, Y., YAMAMOTO, R., YANAGITA, T., KOBAYASHI, H., WADA, A.: "Heterologous increases of cytoplasmic calcium : distinct effects on down-regulation of cell surface sodium channels and sodium channel subunit mRNA levels"British Journal of Pharmacology. 132. 1455-1466 (2001)
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「研究成果報告書概要(欧文)」より
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[Publications] SHIRAISHI, S., YAMAMOTO. R., YANAGITA, T., YOKOO, H., KOBAYASHI, H., UEZONO Y., WADA A.: "Down-regulation of cell surface insulin receptors by sarco(endo)plasmic reticulum Ca2+ATPase inhibitor in adrenal chromaffin cells"Brain Research. 898. 152-157 (2001)
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「研究成果報告書概要(欧文)」より
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[Publications] SHIRAISHI, S., YANAGITA, T., KOBAYASHI, H., UEZONO, Y., YOKOO, H., MINAMI, S., WADA, A.: "Up-regulation of cell surface sodium channels by cyclosporin A, FK 506 and rapamycin in adrenal chromaffin cells"Journal of Pharmacology and Experimental Therapeutics. 297. 657-665 (2001)
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[Publications] MINAMI, K., SEGAWA, K., UEZONO. Y., SHIGA, Y., OGATA, J., SHIGEMATSU, A.: "Adrenomedullin inhibits the pressor effects and decrease in the renal blood flow induced by norepinephrine or angiotensin II in anesthetized rats"Japanese Journal of Pharmacology. 86. 159-164 (2001)
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「研究成果報告書概要(欧文)」より
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[Publications] KAIBARA, M., NAGASE, Y., MURASAKI, O., UEZONO, Y., DOI, Y., TANIYAMA, K.: "GTP-γS-induced Ca2+activated C1-currents : its stable induction by Gqα overexpression in Xenopus oocytes"Japanese Journal of Pharmacology. 86. 244-247 (2001)
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「研究成果報告書概要(欧文)」より
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[Publications] UEZONO Y., NAKAMURA, E., UEDA, Y., SHIBUYA, I., UETA, Y., TOYOHIRA, Y., YANAGIHARA, N., YOKOO, K., KOBAYASHI, H., YANAGITA, T., WADA, A.: "Production of cAMP by adrenomedullin in human oligodendroglial KG1C cells : comparison with calcitonin gene-related peptide and amylin"Molecular Brain Research. 97. 59-69 (2001)
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[Publications] NAGAOKA, E., MINAMI, K., SHIGA, Y., UEZONO, Y., SHIRAISHI, M., AOYAMA, K., SHIGEMATSU, A.: "Tramadol has no effect on renal blood flow - despite increased serum norepinephrine levels - in anesthetized rats : Implication for analgesia in renal insufficiency"Anesthesia and Analgesia. 94. 619-625 (2002)
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[Publications] SHIRAISHI, M., MINAMI, K., UEZONO, Y., YANAGIHARA, N., SHIGEMATSU, A., SHIBUYA, I.: "Inhibitory effects of tramadol on nicotinic acetylcholine receptors in adrenal chromaffin cells and in Xenopus oocytes expressing α7 receptors"British Journal of Pharmacology. 136. 207-216 (2002)
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「研究成果報告書概要(欧文)」より
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[Publications] TSUDA, Y., OKAZAKI, M., UEZONO, Y., OSAJIMA, A., KATO, H., OKUDA, H., OISHI, Y., YASHIRO, A., NAKASHIMA, Y.: "Activation of extracellular signal-regulated kinases is essential for pure transmural pressure-induced proliferation of vascular smooth muscle cells"European Journal of Pharmacology. 446. 15-24 (2002)
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[Publications] MATSUO, K., KAIBARA, M., UEZONO, Y., HAYASHI, H., TANIYAMA, K., NAKANE, Y.: "Involvement of cholinergic neurons in orexin-induced contraction of guinea pig ileum"European Journal of Pharmacology. 452. 105-110 (2002)
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[Publications] SHIRAISHI, M., SHIBUYA, I., MINAMI, K., UEZONO, Y., OKAMOTO, T., UENO, S., UETA, Y., YANAGIHARA, N., SHIGEMATSU, A.: "A neurosteroid anesthetic, alphaxalone, inhibits nicotinic acetylcholine receptors in cultured bovine adrenal chromaffin cells"Anesthesia and Analgesia. 95. 900-906 (2002)
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[Publications] SHIGA, Y., MINAMI, K., SHIRAISHI, M., UEZONO, Y., MURASAKI, O., KAIBARA, M., SHIGEMATSU, A.: "The inhibitory effects of tramadol of muscarinic receptor-induced responses in Xenopus oocytes expressing cloned M3 receptors"Anesthesia and Analgesia. 95. 1269-1273 (2002)
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