1987 Fiscal Year Final Research Report Summary
Molecular Pharmacology of Intracellular Calcium-Receptive Protein Signaling
| Project/Area Number |
61570099
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
General pharmacology
|
|---|
| Research Institution | Mie University |
|---|
Principal Investigator |
TANAKA Toshio Mie University,School of Medicine, Lecturer, 医学部, 講師 (00135443)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
NAKA Michiko Mie University School of Medicine,Assistant, 医学部, 助手 (10093139)
|
|---|
| Project Period (FY) |
1986 – 1987
|
| Keywords | Intracellular Calcium-Receptine Protein / Molecular Pharmacology / Calmodulin / Protein Kinase C / Calcium-dependent Protease / Calpain / Myosin Light Chain Kinase / カルモデュリン阻害剤 |
|---|
| Research Abstract |
Major intracellular calcium-binding protein in vascular smooth muscle is calmodulin, which act through its stimulation of myosin light chain kinase. We found two types of new calmodulin antagonists in this study. One is HT-74,which is a calmodulin antagonist and binds to calmodulin in a manner different from that heretofore reported. Another one is bepridil and it is an antianginal, antiarrhythmic agent with calcium antagonistic properties and is found to bind to calmodulin in the presence of calcium ion and potently inhibit the myosin light chain phosphorylation. These compound may be useful to study calmodulin-dependent calcium signaling. Moreover, we envestigated the interaction between calcium, calmodulin-dependent myosin light chain kinase and calcium-dependent protease (calpain) and the relationship between the myosin light chain kinase and protein kinase C by using isoquinolinesulfonamide derivatives. These results suggest that the calcium-activated proteases may recognize the conformational change of smooth muscle myosin light chain kinase induced by Ca^<2+>-calmodulin complex. And these isoquinolinesulfonamide derivatives should prove to be useful tools for distinguishing between the biological function of Ca^<2+>-activated, phsopholipid-dependent, and calcium, calmodulin-dependent myosin light chain phosphorylation.
|
