胃プロトンポンプの機能と構造
スポンサーリンク
概要
- 論文の詳細を見る
H^+, K^+-ATPase is a proton pump responsible for gastric acid secretion. It actively transports proton and K^+ coupled with the hydrolysis of ATP, resulting in the formation of a 10^6 fold proton gradient across the plasma membrane of parietal cells. The pump belongs to a family of P-type ATPases which include the Na^+ pump (Na^+, K^+-ATPase) and the Ca^<2+> pump (Ca^<2+>-ATPase). This review focuses on the structure-function relationship of this proton pump by using functional antibodies, specific inhibitor(s), a fluorescent reagent and site-directed mutants. First we prepared monoclonal antibodies which modified the functions of the H^+, K^+-ATPase. One of the antibodies, HK2032 inhibited the H^+, K^+-ATPase activity and the chloride conductance in gastric vesicles opened by S-S cross-linking, suggesting that the chloride pathway is in the H^+, K^+-ATPase molecule, and that The H^+, K^+-ATPase is a multi-functional molecule. Other antibody, HK4001 inhibited the H^+, K^+-ATPase activity by inhibiting its phosphorylation step. By using this antibody we found an H^+, K^+-ATPase isoform in the rabbit distal colon. Second we found that scopadulcic acid B, a main ingredient of Paraguayan traditional herb, is an inhibitor specific for the H^+, K^+-ATPase. This compound inhibited the H^+, K^+-ATPase activity by stabilizing the K^+-form of the enzyme. Third we studied the conformational changes of the H^+, K^+-ATPase by observing the fluorescence of FITC-labeled enzyme. H^+, K^+-ATPase did not utilize acetylphosphate instead of ATP as an energy source of active transport, suggesting that the energy transduction system is not common among P-type ATPases. Finally we constructed a functional expression system of the H^+, K^+-ATPase in human kidney cells. By using this functional expression system in combination with site-directed mutagenesis, we studied the significance of amino acid residues in the catalytic centers (a phosphorylation site and an ATP binding site) and the putative cation binding sites. We newly found the sites determining the affinity for cations.
- 公益社団法人日本薬学会の論文
- 1997-07-25
著者
-
Shino Akio
武田薬品工業
-
Asano S
Department Of Pharmacology Faculty Of Pharmaceutical Sciences Osaka University
-
Asano Shoichi
大阪大学 薬 薬理
-
Asano Shoichi
Pharmaceutical Research Division Takeda Chemical Industries Ltd.
-
Shino A
Pharmaceutical Development Division Takeda Chemical Industries Ltd.
-
浅野 真司
富山医科薬科大学遺伝子実験施設
関連論文
- Scopadulcic Acid B, a New Tetracyclic Diterpenoid from Scoparia dulcis L. Its Structure, H^+, K^+-Adenosine Triphosphatase Inhibitory Activity and Pharmacokinetic Behaviour in Rats
- Inhibition by Nitric Oxide of the Uptake of [^3H]Serotonin into Rat Brain Synaptosomes
- Interaction of Orally Administered 5-{3-[((2S)-1,4-Benzodioxan-2-ylmethyl)amino]propoxy} - 1,3-benzodioxole (MKC-242)with 5-HT_ Receptors in Rat Brain
- Ouabain : Induced Cell Proliferation in Cultured Rat Astrocytes
- Ca^2+ Depletion Facilitates Taurine Release in Cultured Rat Astrocytes
- Novel Benzodioxan Derivative, 5-{3 - [((2S) - 1,4 - Benzodioxan - 2 - ylmethyl) amino]propoxy} - 1,3 - benzodioxole HCl (MKC - 242), with a Highly Potent and Selective Agonist Activity at Rat Central Serotonin_ Receptors
- 部位特異的変異導入によるプロトンポンプ阻害剤SCH 28080の結合部位についての考察
- 胃H^+, K^+-ATPase αサブユニットのGlu345のカチオン輸送に対する役割
- Prevention of Gastric Ulcer Relapse Induced by Indomethacin in Rats by a Mutein of Basic Fibroblast Growth Factor
- Role of Endogenous Basic Fibroblast Growth Factor in the Healing of Gastric Ulcers in Rats
- Role of Capsaicin-Sensitive Sensory Neurons and Nitric Oxide in the Protective Effect of Lansoprazole,a Proton Pump Inhibitor,on the Gastric Mucosa in Rats
- Effects of Serotonin_ Agonists on Anoxia-Induced Impairment of Protein Synthesis in Rat Brain Slices
- Establishment and Characterization of a Colonic Epithelial Cell Line MCE301 from Transgenic Mice Harboring Temperature-Sensitive Simian Virus 40 Large T-Antigen Gene
- Development and Characterization of Conditionally Immortalized Gastric Epithelial Cell Lines from Transgenic Rats Harboring Temperature-Sensitive Simian Virus 40 Large T-antigen Gene
- Stable Expression of Gastric Proton Pump Activity at the Cell Surface
- Expression of ATP1AL1, a Non-Gastric Proton Pump, in Human Colorectum
- Is Rabbit CLCA1 Related to the Basolateral Ca^-Dependent Cl^- Channel of Gastric Parietal Cells?
- 胃酸分泌プロトンポンプの構造と機能 (特集 膜輸送ナノマシーンの構造・作動機構と制御)
- 胃酸分泌プロトンポンプの機能と膜ダイナミクス
- 消化管系 消化管上皮組織機能とイオンチャネル (〔2002年〕6月第5土曜特集 イオンチャネルの最前線) -- (臓器でのイオンチャネルの働きと疾患)
- 2SE6 部位特異的変異導入法による胃プロトンポンプのイオン認識、輸送部位の推定
- Significance of Lysine/Glycine Cluster Structure in Gastric H^+, K^+-ATPase
- Mutational Analysis of the Putative K^+-Binding Site on the Fourth Transmembrane Segment of the Gastric H^+, K^+-ATPase
- 胃プロトンポンプの構造と機能
- 胃プロトンポンプの機能と構造
- 抗体を使った胃H+,K+-ATPア-ゼの構造と機能の解析
- 胃酸分泌の調節機構解明と胃プロトンポンプを標的とする創薬を目指した試験管内評価系の確立
- Role of Capsaicin-Sensitive Sensory Neurons and Nitric Oxide in the Protective Effect of Lansoprazole, a Proton Pump Inhibitor, on the Gastric Mucosa in Rats