| Project/Area Number |
11470428
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Surgical dentistry
|
|---|
| Research Institution | HOKKAIDO UNIVERSITY |
|---|
Principal Investigator |
SUZUKI Kuniaki Hokkaido Univ. Grad. School of Dental Medicine, Prof., 大学院・歯学研究科, 教授 (40133748)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
DEYAMA Yoshiaki Hokkaido Univ. Grad. School of Dental Medicine, Inst., 大学院・歯学研究科, 助手 (80271667)
YOSHIMURA Yoshitaka Hokkaido Univ. Grad. School of Dental Medicine, Inst., 大学院・歯学研究科, 助手 (30230816)
HIROAKI Toshihumi Hokkaido Univ. Grad. School of Eng., Asso. Prof., 大学院・工業研究科, 助教授 (10125346)
IIDA Akira Hokkaido Univ. Grad. School of Dental Medicine, Inst., 大学院・歯学研究科, 助手 (90292036)
|
|---|
| Project Period (FY) |
1999 – 2001
|
| Project Status |
Completed (Fiscal Year 2001)
|
| Budget Amount *help |
¥10,600,000 (Direct Cost: ¥10,600,000)
Fiscal Year 2001: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2000: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1999: ¥6,000,000 (Direct Cost: ¥6,000,000)
|
|---|
| Keywords | Na, K-ATPase / alkaline phosphatase / isoflurane / sevofluraae / halothane / ketamine / benzodiazepin / droperidol / Na,K-ATPase / ベンゾジアゼピン / フルマゼニル / 全身麻酔薬 / 揮発性麻酔薬 / sodium dodecyl sulfate / ゲルろ過クロマトグラフィー / アイソザイム / サブユニット間の相互作用 / 表面構造 / イソフルラン / NMR |
|---|
| Research Abstract |
l) We studied the effects of volatile anesthetics, benzodiazepines, ketamine and droperidol on Na^+, K^+-ATPase activity; (1) All of anesthetics except fentanyl inhibited Na, K-ATPase activity and its partial reactions in a dose dependent manner. There were certain patterns, characteristic of each category of the anesthetics, in the order of IC50 values of Na, K-ATPase activity and its partial reactions. Effects of the anesthetics on the phosphointermediate (EP) formation differed among the anesthetics. Benzodiazepine inhibited the EP formation, whereas isoflurane and ketamine did not. The sensitivity of EP to potassium was increased by ketamine but was decreased by isoflurane. These findings suggest that the inhibitory mechanisms of general anesthetics against Na, K-ATPase activity are diverse among the categories of anesthetics. (2) Benzodiazepines inhibited Na, K-ATPase activity by inhibiting the step after EP formation and the inhibition was partialy reversible, and that binding sites of Na, K-ATPase for benzodiazepines were different from those of GABAA receptor.(3)Droperidoi inhibited the ATPase activity of Na, K-ATPase by decreasing the rate of dephosphorylation of EP and that the inhibition was reversible. 2) To better understand the effects of volatile anesthetics on proteins, we studied the effects of volatile anesthetics on Na^+, K^+-ATPase that requires lipids for activity and alkaline phosphatase (ALP) that does not require lipids for activity. The results suggested that lipid is not always necessary for the action of volatile anesthetics, and that the action of volatile anesthetics is influenced by the slight difference of isozymes, for example, primary structure and by the change of slight subunit -subunit interaction or alteration of surface structure caused by SDS.
|
