1999 Fiscal Year Final Research Report Summary
Pharmacological studies on bioactive compounds isolated from marine organisms
| Project/Area Number |
10470479
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Tohoku University |
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Principal Investigator |
OHIZUMI Yasushi Graduate School of Pharmaceutical Sciences, Tohoku University, Professor, 大学院・薬学研究科, 教授 (00006355)
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| Co-Investigator(Kenkyū-buntansha) |
NAKATANI Keigo Graduate School of Pharmaceutical Sciences, Tohoku University, Research Associate, 大学院・薬学研究科, 教務職員 (60281979)
MATSUNAGA Kimihiro Graduate School of Pharmaceutical Sciences, Tohoku University, Research Instructor, 大学院・薬学研究科, 助手 (90222306)
NAKAHATA Norimichi Graduate School of Pharmaceutical Sciences, Tohoku University, Research Instructor, 大学院・薬学研究科, 助教授 (60045804)
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| Project Period (FY) |
1998 – 1999
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| Keywords | goniodomin A / xestoquinone / gramine rerivative / maitotoxin / amphidinolide B / actomyosin ATPase / CaィイD12+ィエD1 release / nerve growth factor |
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| Research Abstract |
Goniodomin A has been shown to cause the conformational change of actin to modify actomyosin ATPase activity. This compound increased and decreased actomyosin ATPase activity, probably through the stimulatory and inhibitory sites on actin, respectively. The troponin/tropomyosin complex binds to actin to inhibit the goniodomin A-induced enhancement of actomyosin ATPase activity, probably by the affecting the stimulatory site on the molecule. Xestoquinone, isolated from a sea sponge Xestospongia sapra, caused a concentration-dependent CaィイD12+ィエD1 release through sulfhydryl modification from skeletal muscle sarcoplasmic rericulum. 5,6-Dibromo-1,2-dimethylgramine evoked CaィイD12+ィエD1 release from skeletal muscle sarcoplasmic reticulum through ryanodine receptors in a concentration-dependent manner. Study of structure-activity relationship for CaィイD12+ィエD1 release indicated that 1-methylation and/or both 5- and 6-bromination are important for CaィイD12+ィエD1 release. Maitotoxin induced a profound increase in CaィイD12+ィエD1 influx in an extracellular CaィイD12+ィエD1-dependent manner. Maitotoxin as well as A-23187 and dubutyryl cyclic AMP caused an acceleration of nerve growth factor (NGF) production in C6-BU-1 cells, as determined by NGF enzyme immunoassay. Maitotoxin activated a voltage-insensitive CaィイD12+ィエD1 channel and accelerated NGF production mediated through a CaィイD12+ィエD1 signaling pathway in C6-BU-1 glioma cells. Amphidinolide B enhanced an interaction of actin and myosin directly and increased CaィイD12+ィエD1 sensitivity of the contractile apparatus mediated through troponin/tropomyosin system, resulting in an increase in the ATPase activity and thus enhanced the contractile response of myofilament.
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