1994 Fiscal Year Final Research Report Summary
New assay systems for the development of inhibitory drugs against activated mast cell function
| Project/Area Number |
04557108
|
|---|
| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Biological pharmacy
|
|---|
| Research Institution | KYOTO UNIVERSITY |
|---|
Principal Investigator |
ICHIKAWA Atsushi Kyoto University, Physiological Chemistry, Professor, 薬学部, 教授 (10025695)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
HARA Kiyoto Kissei Medicine, Research worker, 創薬品研究所, 研究員
KURASHINA Kichi Kissei Medicine, the head, 創薬品研究所, 所長
KUDO Ichiro Univ.of Tokyo, Fac.Pharmaceutical Sci., Associate Professor, 薬学部, 助教授 (30134612)
INOUE Keizo Univ.of Tokyo, Fac.Pharmaceutical Sci., Professor, 薬学部, 教授 (30072937)
FUKUI Tetsuya Kyoto University, Physiological Chemistry, Associate Professor, 薬学部, 助教授 (90111971)
|
|---|
| Project Period (FY) |
1992 – 1994
|
| Keywords | mast cell function / inflammation / histidine decarboxylase / histamine / phospholipase A_2 / arachidonate |
|---|
| Research Abstract |
(Kyoto University)
We have isolated mouse histidine decarboxylase (HDC), and cloned its cDNA and partial genomic DNA.Mouserecombinant HDC expressed in Baculovirus-SF9 cells has a 74 kDa in size mostly present in the particulate fraction with a low enzyme activity, whereas a C-termial delated mutant recombinant HDC which is a homodimer of 54 kDa subunit is a fullly active enzyme Present in soluble fraction. Particulate recombinant 74 kDa HDC was interconvertedinto the soluble form having intensified activity by porcine pancreatic elastase treatment. We further obtained that mouse HDC in mastocytoma cells was specifically induced by treatment with a combination of dexamethasone and TPA,of Ca^<2+> and cAMP.Furthermore, the regulatory elements involved in the increased transcription of the HDC gene with dexamethasone/TPA of Ca^<2+>/cAMP were determined in the promoter regions of the genomic DHA clone of the mouse HDC gene. These results contribute the study for developing a new type drug which acts on the regulation of histamine synthesis in histamine-producing cells such as mast cells.
(Tokyo Univercity)
We detect at least two kinda of phospholipase A_2 in rat and mouse mast cells. One of the enzyme, c-phospholipase A_2 was phospholylated shorty after cell stimulation, and this process may play an importaut role for releasing arachidonate during cell activation. Type II secretory phospholipase A_2 was secreted and bound to the surface membrane when mast cells were stimulated. It was suggested that the enzyme may be involved in the process leading to release of histamine. Inhibitors of either c-or secretory phospholipases A_2 may be useful for suppression of mast cell activation.
|
