STUDIES ON CAPACITATIVE CALCIUM ENTRY IN CELLULAR SIGNAL TRANSDUCTION

细胞信号转导中电容性钙进入的研究

• 批准号: 05680619
• 负责人: TAKEMURA Haruo
• 金额: $ 1.34万
• 依托单位: SAPPORO MEDICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05680619/
• 关键词: Cellular signal transduction; Calcium ion; Calcium entry; Intracellular calcium pool; Thapsigargin; thapsigargin

Ca^<2+> entry coupled to intracellular Ca^<2+> pool (ICP), which is called "capacitative Ca^<2+> entry", was investigated in rat glioma C6 cells, human leukemia Jurkat cells and cultured rat hepatocytes. In C6 cells, the sustained increase in cytosolic free Ca^<2+> concentration ([Ca^<2+>]_i)induced by bombesin and thapsigargin (TG), a microsomal Ca^<2+>-ATPase inhibitor, was abolished in the presence of tetrandrine, a receptor-operated Ca^<2+> channel (ROC) inhibitor. The pretreatment with pertussis toxin (IAP), phorbol ester, protein kinase C (C-kinase) inhibitor, tyrosine kinase inhibitor or cytoskeleton inhibitor did not affect [Ca^<2+>] _i induced by bombesin and TG.In Jurkat cells, at least two kinds of ICPs, both of which are IP_3-and lysophosphatic acid (LPA)-sensitive, existed and LPA sensitive-ICP did not relate to "capacitative Ca^<2+> entry." In cultured hepatocytes, TG did not cause Ca^<2+> oscillation. Ruthenium red inhibited Ca^<2+> oscillation induced by vasopressin but not [Ca^<2+>] _i induced by TG.We suggest that IAP-sensitive GTP-binding protein, C-kinase, tyrosine kinase and cytoskeleton are not involved in the activation of "capacitative Ca^<2+> entry" and that "capacitativeCa^<2+> entry" does not relate to Ca^<2+> oscillation. Furthermore, there seems to exist two kinds of ICPs, one of which couples to "capacitative Ca^<2+> entry."

在大鼠脑胶质瘤C6细胞、人白血病Jurkat细胞和培养的大鼠肝细胞中，研究了与细胞内钙池(ICP)偶联的钙离子内流，称为“容量性钙内流”。在C6细胞中，蛙皮素和微粒体钙通道(ROC)阻断剂thapsigargin(TG)引起的胞浆游离钙浓度([Ca^&lt；2+&gt；]i)的持续升高可被受体操作的钙通道(ROC)阻断剂粉防己碱所阻断。百日咳毒素(IAP)、佛波酯、蛋白激酶C(C-Kinase)抑制剂、酪氨酸激酶抑制剂或细胞骨架抑制剂不影响蛙皮素和TG诱导的[Ca^&lt；2+&gt；]_i。Jurkat细胞中至少存在两种对IP_3和溶血磷酸(LPA)敏感的ICP，LPA敏感的ICP与“容量性钙进入”无关。在培养的肝细胞中，TG不引起Ca~(2+)&gt；振荡。Ru红抑制后叶加压素诱导的钙振荡，但不抑制TG诱导的[Ca^&lt；2+&gt；]_i。提示IAP敏感的GTP结合蛋白、C-激酶、酪氨酸激酶和细胞骨架不参与“容积性钙内流”的激活，“容量性钙内流”与钙内皮细胞的振荡无关。此外，似乎存在两种ICP，其中一种与“容量性钙离子通道”相耦合。

项目成果

竹村晴夫 他: "T細胞における細胞情報伝達物質としてのsphingosineのCa^<2+>動員作用" Japan.J.Pharmacol.65 Suppl.I. 253- (1995)

Haruo Takemura等人：“鞘氨醇作为T细胞中的细胞信号传递者的Ca 2+ 动员效应”Japan.J.Pharmacol.65 Suppl.I.253-(1995)。

坂野晶司、竹村晴夫 他: "イノシトールリン酸に関与しないsphingosineのカルシウム動員作用" 薬物活性シンポジウム要旨集. 264-269 (1994)

Shoji Sakano、Haruo Takemura 等人：“不涉及磷酸肌醇的鞘氨醇的钙动员作用”药物活性研讨会摘要 264-269 (1994)。

Takemura, H.: "Ca^<2+>-mobilizing actions of sphingosine, as a second messenger, in T cells." Japan.J.Pharmacol.65(Suppl.I). 253 (1995)

Takemura, H.：“鞘氨醇作为第二信使在 T 细胞中的 Ca^2 动员作用。”

Sakano, S.: "Inhibitory effects of tetrandrine and hernandezine on receptor-operated Ca^<2+> entry in rat glioma C6 cells." Japan.J.Pharmacol.65(Suppl.I). 87 (1995)

Sakano, S.：“粉防己碱和赫南地嗪对大鼠神经胶质瘤 C6 细胞中受体操纵的 Ca^2 进入的抑制作用。”

Takemura,H.: "β-Adrenergic receptor-mediated calcium mobilization in the human Jurkat T cell line." LIfe Sci.56. 1443-1454 (1995)

Takemura, H.：“人类 Jurkat T 细胞系中 β-肾上腺素受体介导的钙动员。” 1443-1454 (1995)。