| Project/Area Number |
04557107
|
|---|
| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Biological pharmacy
|
|---|
| Research Institution | The University of Tokyo (Faculty of Pharmaceutical Sciences) (1993)
Tokyo Institute of Technology (1992) |
|---|
Principal Investigator |
KATADA Toshiaki The University of Tokyo, Faculty of Pharmaceutical Sciences, Department of Physiological Chemistry, Professor, 薬学部, 教授 (10088859)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
NISHINA Hiroshi Tokyo Institute of Technology, Department of Life Science, Research fellow, 生命理工学部, 助手 (60212122)
TAKAHASHI Katsunobu Tokyo Institute of Technology, Department of Life Science, Research fellow, 生命理工学部, 助手 (40183850)
HOSHINO Shin-ichi The University of Tokyo, Department of Physiological Chemistry, Research fellow, 薬学部, 助手 (40219168)
HAZEKI Osamu The University of Tokyo, Department of Physiological Chemistry, Research fellow, 薬学部, 助手 (80142751)
石井 孝司 帝人株式会社, 生物医学第一研究所, 研究員
|
|---|
| Project Period (FY) |
1992 – 1993
|
| Project Status |
Completed (Fiscal Year 1993)
|
| Budget Amount *help |
¥11,600,000 (Direct Cost: ¥11,600,000)
Fiscal Year 1993: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1992: ¥8,100,000 (Direct Cost: ¥8,100,000)
|
|---|
| Keywords | GTP-binding proteins / Pertussis toxin / Membrane receptors / ADP-ribosylation / Signal transduction / GTPase / Mastoparan / 抗鬱薬 |
|---|
| Research Abstract |
GTP-binding proteins consisting of alpha-, beta- and gamma-subunits (G proteins) carry signals from membrane receptors to effectors such as enzymes or ion channels. Recent studies have indicated that several peptides, such as mastoparan, directly interact with G proteins resulting in the activation of the signal-coupling proteins in manners similar to receptors stimulated by agonists.
In the present studies, possible interactions of various venom peptides (and related compounds) with G proteins and/or membrane receptors were studied in reconstituted phospholipid vesicles. Mast cell-degranulating (MCD) peptide stimulated the steady-state rate of GTP hydrolysis catalyzed by the reconstituted G proteins. Synthetic D-MCD peptide, the optical isomer of MCD peptide, was also effective in the activation of G proteins as L-MCD peptide. The stimulations by L- and D-peptides were both abolished in G proteins that had been ADP-ribosylated by pertussis toxin. In comparison of the amino acid sequences of various peptides tested, the extent of the activation of G proteins appeared to be correlated with the number of basic amino acid residues in the alpha-helix of peptides. These results suggest that cationic clusters at one side of the alpha-helical surface are more important in the direct activation of G proteins than a specific, alpha-helical structure. Moreover, mastoparan induced conversion of a high- and a low-affinity states of membrane receptors for agonists to a new middle-affinity state, which was resulted from coupling of the receptors with G proteins. Thus, the various activities G proteins appeared to be utilizable for elucidation of some types of drug screening.
|
