Possible involvement of CaィイD12+ィエD1-signaling transferred to mitochondria in release of ATP as an autacoid

CaD12+D1 信号可能参与转移至线粒体并作为自体物质释放 ATP

• 批准号: 10670102
• 负责人: KATSURAGI Takeshi
• 金额: $ 1.34万
• 依托单位: Fukuoka Universiry
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670102/
• 关键词: α, β-Methylene ATP; ATP release; ileal smooth muscle; Ins(1, 4, 5)PィイD23ィエD2; vas deferens; ryanodine receptor; P2-purinoceptors; CaィイD12+ィエD1-signaling; α,β-MethyleneATP; 細胞内シグナル伝達経路; Angiotensin II; 培養結腸紐平滑筋細胞; α, β-Methylene ATP; ATP release; ileal smooth muscle; Ins(1, 4, 5)PィイD23ィエD2; vas deferens; ryanodine receptor; P2-purinoceptors; CaィイD12+ィエD1-signaling; α,β-MethyleneATP; 細胞内シグナル伝達経路; Angiotensin II; 培養結腸紐平滑筋細胞

ATP is extracellularly released as an autocine/paracrine and served as a functional modulator via stimulating P2-receotors of cell types.Hitherto, however, it remains unprovided evidence for the release mechanism and intracellular source of ATP. The research project was planed to clarify the existence of CaィイD12+ィエD1-signal pathway from endoplasmic reticulum (ER) to mitochondria in the release for ATP. In 1998, we demonstrated in ideal longitudinal smooth muscles of guinea-pigs that the release of ATP evoked by stimulating P2Y-purioceptors with α, β-methylene ATP (α, β-mATP) resulted from increase of Ins(1, 4, 5)PィイD23ィエD2 production via activation of phospholipase C and subsequently, from enhanced release of CaィイD12+ィエD1 from CaィイD12+ィエD1 storage sites. From the study during 1999 carried out with the vas deferens smooth muscles, it has been considered the possibility that α, β-mATP stimulates P2X-purinodeptors and, then activates ryanodine receptors on endoplasmic reticulum (ER), like caffeine, and the subsequent release of CaィイD12+ィエD1 from ER generating the release of ATP. The evoked release of ATP seen in both smooth muscles was interfered with mitochondrial inhibitors such as rotenone. Accordingly, it is suggested that release of ATP couples with CaィイD12+ィエD1-signal pathways from ER to mitochondria. The viewpoint will be clarified in a further analysis using fluorescent CaィイD12+ィエD1-probes to measure [CaィイD12+ィエD1]i in cultured rat hepatocytes without contractility.

ATP在细胞外释放为自动蛋白/旁分泌，并通过刺激细胞类型的P2-eceotors作为功能调节剂。但是，它仍然是释放机制和ATP细胞内源的证据。该研究项目计划阐明从内质网（ER）到线粒体的CAIY D12+IE D1信号途径的存在。在1998年，我们在豚鼠的理想纵向平滑肌肉中证明了ATP的释放是通过用α，β-甲基ATP（α，β-MATP）刺激P2Y-Purioceptor的刺激P2Y-Purioceptor，这是由INS释放（1，4，5）PIY D2IE D2IE D2生产和磷酸化酶的激活量的增强而引起的。 D12+IE D1来自CAIY D12+IE D1存储站点。 From the study during 1999 carried out with the vas deferens smooth muscles, it has been considered the possibility that α, β-mATP stimulates P2X-purinodeptors and, then activates ryanodine receptors on endoplasmic reticulum (ER), like caffeine, and the subsequent release of Caiy D12+Ie D1 from ER generating the release of ATP.在两种平滑肌中看到的ATP的诱发释放都干扰了线粒体抑制剂，例如烤面包酮。据此，建议释放从ER到线粒体的CAII D12+IYE D1信号途径的ATP夫妇的释放。该观点将在进一步的分析中使用荧光CAII D12+IYE D1探针进行进一步的分析，以测量培养的大鼠肝细胞中没有收缩性的大鼠肝细胞中的[CAII D12+IYE D1] I。