2000 Fiscal Year Annual Research Report

体液・循環調節に関与するペプチドホルモン受容体に関する比較分子生物学的研究(塩類細胞の分子解剖と分化誘導機構の解明)

Research Project

Project/Area Number	09102008
Research Institution	Tokyo Institute of Technology
Principal Investigator	広瀬茂久東京工業大学, 大学院・生命理工学研究科, 教授 (10134199)
Co-Investigator(Kenkyū-buntansha)	萩原啓実東京工業大学, 生物実験センター, 助教授 (90189465) 竹井祥郎東京大学, 海洋研究所, 教授 (10129249)
Keywords	循環調節 / 内向き整流性Kチャネル / 恐山 / 塩類細胞 / ウナギ / 広塩性魚類 / 酸性適応 / ウグイ
Research Abstract	比較分子生物学的なアプローチから循環系の恒常性維持機構の解明に新視点を導入しつつある。本年度も引き続き,淡水・海水の両方に適応できるウナギと高度な酸性適応能を有する恐山ウグイの系を中心に解析を進め以下の成果を得た。1)新規Kチャネル(Kir7.1)の生理機能:ウナギの海水適応に重要な分子の解析から見つけたKir7.1が生理学上極めて重要で,古くから探し求められていたNa,K-ATPaseのパートナー分子らしいことを示したのに続いて本年度は,Kir7.1遺伝子の構造を決定し,プロモーターの解析から極めて複雑な発現調節を受けていること及びNa^+,K^+-ATPaseの増減とよく対応した変化を示すことを明らかにした。さらに大変興味深いことに,Kir7.1と似た膜トポロジーを有する大きな蛋白質ファミリーが存在することを見つけ,生理機能を解明中である。2)酸性適応機構の解明:驚くべき酸性(pH3.5)適応能を有する恐山湖ウグイを用いて,酸性適応に重要な分子を探索し,Carbonic anhydraseとその下流に位置するNa^+/H^+交換体(NHE)及びNa^+/HCO_3^-共輸送体(NBC)が重要な働きをしていることをつきとめた。しかもそれらがエラの塩類細胞に極性を持って存在していること,すなわちNHEはApical側に,NBCはBasolateral側に局在していることを明らかにした。塩類細胞はこれら分子の助けを借りて,H^+を外界に徘出し,重炭酸イオンを血中に供給することにより体液の酸性化を防いでいるものと推定される。3)塩類細胞の新機能とUrea transporter(UT):ウナギの海水型塩類細胞からUTをクローニングすることに成功した。さらに,サメの尿素を用いたユニークな浸透圧調節機構を明らかにするため,UTとその調節因子と考えられる後葉ホルモンをクローン化するとともに,UTの分布を免疫組織化学により明らかにした。

Research Products
(19 results)

All Other

All Publications (19 results)

[Publications] Yamashita,Y. et al.: "Concentration of mRNA for the natriuretic peptide receptor-C in hypertrophic chondrocytes of the fetal mouse tibia."J.Biochem.. 127. 177-179 (2000)
[Publications] Yada,T. et al.: "Effects of desacetyl-α-MSH on lipid mobilization in teh raibou trout, Oncohynchus mykiss"Zool.Sci.. 17. 1123-1127 (2000)
[Publications] Tanaka,N. et al.: "Elafin is induced in epidermis in skin desorders with dermal neutrophilic infiltration : interleukin-1 beta and tumour necrosis factor-alpha stimulate its secretion in vitro."Br.J.Dermatol.. 143. 728-732 (2000)
[Publications] Tanaka,N. et al.: "Levels of proelafin peptides in the sera of the patients with generalized pustular psoriasis and pustulosis palmoplantaris."Acta Derm.Venereol.. 80. 102-105 (2000)
[Publications] Suzuki,Y. et al.: "Localization of porcine trappin-2(SKALP/elafin) in trachea and large intestine by in situ hybridization and immunohistochemistry."Histochem.Cell Biol.. 114. 15-20 (2000)
[Publications] Otsuka,E. et al.: "IRole of ascorbic acid in the osteoclast formation : induction of osteoclast differentiation factor with formation of the extracellular collagen matrix.Role of ascorbic acid in the osteoclast formation : induction of osteoclast differentiation factor with formation of the"Endocrinology. 141. 3006-3011 (2000)
[Publications] Ookata,K. et al.: "Localization of inward rectifier potassium Channel Kir7.1 in the basal membrane of distal nephron."J.Am.Soc.Nephrol.. 11. 1987-1994 (2000)
[Publications] Nakamura,N. et al.: "Complex structure and regulation of expression of the rat gene for inward rectifier potassium channel Kir7.1."J.Biol.Chem. 275. 28276-28284 (2000)
[Publications] Nagase,T. et.al.: "Crouzon syndrome with acanthosis nigricans : case report and mutational analysis."Cleft Palate Craniofac.J.. 37. 78-82 (2000)
[Publications] Koyama,A. et al.: "Nitric oxide accelerates the ascorbic acid-induced osteoblastic differentiation of mouse stromal ST2 cells by stimulating the production of prostaglandin E(2)."Eur.J.Pharmacol.. 391. 225-231 (2000)
[Publications] Inoue,A. et al.: "The transcript for a novel protein with a zinc finger motif is expressed at specific stages of mouse spermatogenesis."Biochem.Biophys.Res.Commun.. 273. 398-403 (2000)
[Publications] Inoue,A. et al.: "Vasoactive peptide-regulated gene expression during osteoblastic differentiation [In Process Citation]."J.Cardiovasc.Pharmacol.. 36. S286-S289 (2000)
[Publications] Honda,S. et.al.: "Multiplicity, structures, and endocrine and exocrine natures of eel fucose-binding lectins."J.Biol.Chem.. 275. 33151-33157 (2000)
[Publications] Furutani,Y. et al.: "A simple assay and histochemical localization of transglutaminase activity using a derivative of green fluorescent protein as substrate"J.Histochem.Cytochem.. 49. 247-258 (2000)
[Publications] Ookata,K. et al.: "Distribution of stanniocalcin I in the apical membranes of the distal nephron of rat kidney and its regulation by vitamin D3"Exp.Nephrol. (In press). (2000)
[Publications] Takei,Y. et.al.: "Role of the renin-angiotensin system in drinking of seawater-adapted eels, Anguilla japonica : A reevaluation."Am.J.Physiol.. 279. R1105-R1111 (2000)
[Publications] Takei Y. et al.: "Antidipsogenic effect of eel bradykinin in the eel, Anguilla japonica."Am.J.Physiol.,. (in press). (2001)
[Publications] Takei,Y.: "Does the natriuretic peptide system exist throughout the animal and plant kingdom?"Comp.Biochem.Physiol.. (in press). (2001)
[Publications] Takei,Y. et al.: "The natriuretic peptide system in the eel : a key endocrine system for euryhalinity."Am.J.Physiol.. 280(in press). (2001)

2000 Fiscal Year Annual Research Report

体液・循環調節に関与するペプチドホルモン受容体に関する比較分子生物学的研究(塩類細胞の分子解剖と分化誘導機構の解明)

Principal Investigator

広瀬 茂久 東京工業大学, 大学院・生命理工学研究科, 教授 (10134199)

Research Products

[Publications] Yamashita,Y. et al.: "Concentration of mRNA for the natriuretic peptide receptor-C in hypertrophic chondrocytes of the fetal mouse tibia."J.Biochem.. 127. 177-179 (2000)

[Publications] Yada,T. et al.: "Effects of desacetyl-α-MSH on lipid mobilization in teh raibou trout, Oncohynchus mykiss"Zool.Sci.. 17. 1123-1127 (2000)

[Publications] Tanaka,N. et al.: "Elafin is induced in epidermis in skin desorders with dermal neutrophilic infiltration : interleukin-1 beta and tumour necrosis factor-alpha stimulate its secretion in vitro."Br.J.Dermatol.. 143. 728-732 (2000)

[Publications] Tanaka,N. et al.: "Levels of proelafin peptides in the sera of the patients with generalized pustular psoriasis and pustulosis palmoplantaris."Acta Derm.Venereol.. 80. 102-105 (2000)

[Publications] Suzuki,Y. et al.: "Localization of porcine trappin-2(SKALP/elafin) in trachea and large intestine by in situ hybridization and immunohistochemistry."Histochem.Cell Biol.. 114. 15-20 (2000)

[Publications] Ookata,K. et al.: "Localization of inward rectifier potassium Channel Kir7.1 in the basal membrane of distal nephron."J.Am.Soc.Nephrol.. 11. 1987-1994 (2000)

[Publications] Nakamura,N. et al.: "Complex structure and regulation of expression of the rat gene for inward rectifier potassium channel Kir7.1."J.Biol.Chem. 275. 28276-28284 (2000)

[Publications] Nagase,T. et.al.: "Crouzon syndrome with acanthosis nigricans : case report and mutational analysis."Cleft Palate Craniofac.J.. 37. 78-82 (2000)

[Publications] Koyama,A. et al.: "Nitric oxide accelerates the ascorbic acid-induced osteoblastic differentiation of mouse stromal ST2 cells by stimulating the production of prostaglandin E(2)."Eur.J.Pharmacol.. 391. 225-231 (2000)

[Publications] Inoue,A. et al.: "The transcript for a novel protein with a zinc finger motif is expressed at specific stages of mouse spermatogenesis."Biochem.Biophys.Res.Commun.. 273. 398-403 (2000)

[Publications] Inoue,A. et al.: "Vasoactive peptide-regulated gene expression during osteoblastic differentiation [In Process Citation]."J.Cardiovasc.Pharmacol.. 36. S286-S289 (2000)

[Publications] Honda,S. et.al.: "Multiplicity, structures, and endocrine and exocrine natures of eel fucose-binding lectins."J.Biol.Chem.. 275. 33151-33157 (2000)

[Publications] Furutani,Y. et al.: "A simple assay and histochemical localization of transglutaminase activity using a derivative of green fluorescent protein as substrate"J.Histochem.Cytochem.. 49. 247-258 (2000)

[Publications] Ookata,K. et al.: "Distribution of stanniocalcin I in the apical membranes of the distal nephron of rat kidney and its regulation by vitamin D3"Exp.Nephrol. (In press). (2000)

[Publications] Takei,Y. et.al.: "Role of the renin-angiotensin system in drinking of seawater-adapted eels, Anguilla japonica : A reevaluation."Am.J.Physiol.. 279. R1105-R1111 (2000)

[Publications] Takei Y. et al.: "Antidipsogenic effect of eel bradykinin in the eel, Anguilla japonica."Am.J.Physiol.,. (in press). (2001)

[Publications] Takei,Y.: "Does the natriuretic peptide system exist throughout the animal and plant kingdom?"Comp.Biochem.Physiol.. (in press). (2001)

[Publications] Takei,Y. et al.: "The natriuretic peptide system in the eel : a key endocrine system for euryhalinity."Am.J.Physiol.. 280(in press). (2001)

広瀬茂久東京工業大学, 大学院・生命理工学研究科, 教授 (10134199)