The practicability of phosphatase inhibitors for research reagents.

磷酸酶抑制剂研究试剂的实用性。

• 批准号: 03556040
• 负责人: KARAKI Hideaki
• 金额: $ 10.43万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research (B)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03556040/
• 关键词: phosphatase; smooth muscle; ion channel; cytoskeleton; ホスファターゼ; 平滑筋; 海産毒; ホスファタ-ゼ

It was known that there are four phosphatase inhibitors, such as okadaic acid, calyculin-A, tautomycin and microcystin-LR.At first, we investigated the effects of these compounds on various types of phosphatase acitivities. okadaic acid and microcystin-LR selectively inhibited type 2A phosphatase purified from bovine cardiac muscle at low concentration. At high concentration, however, these compounds also inhibited type 1 phosphatase purified from turkey gizzard. In contrast, calyculin-A and tautomycin nonselectively inhibited type 1 and type 2A phosphatase. These compounds did not affect on type 2B and 2C phosphatases.We inivestigated the physiological role of phosphatase on contractile elements, ion channels and cell structure, and clarified that the regulatory phosphatase of contractile elements may have type 1 like characterization for phosphatase inhibitors in smooth muscle, and that calyculin-A may facilitate the opening of the L-type Ca channels through the protein kinase C-dependent phosphorylation system in smooth muscle cells of guinea-pig taenia coli and that the changes in cytoskeletal structure may be caused by disturbing the balance of phosphorylation and dephosphorylation in the culured A10 cells.

目前已知的磷酸酶抑制剂有冈田酸、calyculin-A、互变霉素和微囊藻毒素-LR四种。冈田酸和微囊藻毒素-LR在低浓度下选择性抑制从牛心肌中纯化的2A型磷酸酶。然而，在高浓度下，这些化合物也抑制从火鸡砂囊中纯化的1型磷酸酶。相反，calyculin-A和互变霉素非选择性抑制1型和2A型磷酸酶。这些化合物对2B和2C型磷酸酶无影响，我们研究了磷酸酶对收缩元件、离子通道和细胞结构的生理作用，阐明了收缩元件的调节磷酸酶可能具有平滑肌磷酸酶抑制剂的1型特征，Calyculin-A可能通过蛋白激酶C依赖的磷酸化系统促进豚鼠平滑肌细胞L-型Ca通道的开放。细胞骨架结构的改变可能是由于磷酸化与去磷酸化平衡失调所致。

项目成果

Usuki,T.,Obara,K.,Someya,T.,Ozaki,H.,Karaki H.,Fusteani,N.and Yabu,H.: "Calyculin A increases voltage-dependent inward current in smooth muscle cells isolated from guinea pig taenia coli." Experientia. 47. 939-941 (1991)

Usuki,T.、Obara,K.、Someya,T.、Ozaki,H.、Karaki H.、Fusteani,N. 和 Yabu,H.：“Calyculin A 增加从几内亚分离的平滑肌细胞中的电压依赖性内向电流

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UBUKATA,M.,程X-C.,ISOBE,M.