Participation of calcium ion in ATP release from the vascular endothelial cells.

钙离子参与血管内皮细胞释放 ATP。

• 批准号: 09670112
• 负责人: SHINOZUKA Kazumasa
• 金额: $ 1.92万
• 依托单位: Mukogawa Women's University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670112/
• 关键词: ATP; Rat caudal artery; alpha1-adrenoceptor; Calcium ion; Gap junction; Nitric Oxide; Cultured endothelial cells; 血管内皮細胞; _<α1>アドレナリン受容体; ノルアドレナリン

Pharmacological studies on the mechanism of ATP-release :In the the rat caudal arteries, noradrenaline (NA) evoked a significant release of ATP and its metabolites, which was abolished by prazosin, Ca^<2+> free and rubbing of endothelium. The release of ATP was increased by the sodium-potassium exchange solution. But, 40 mM KC1 solution and hypertonic solution reduced the release of ATP.Therefore, depolarization may facilitate the release of ATP.It is reported that the function of gap junction is prevented by hyperosmolarity. L-heptanol, gap junction inhibitor, abolished the release of ATP.These suggest that the mechanisms of ATP-release is closely associated with Ca^<2+> influx and gap junction in voltage depent manner.Microscopic studies on the mechanism of ATP-release :In the rat caudal arteries, NA clearly raised intracellular Ca^<2+> levels in the endothelial and smooth muscle cells. On the other hand, in the cultured endothelial cells isolated from the rat caudal artery, NA did n … More ot raise intracellular Ca^<2+> level. Also, NA did not evoke the release of ATP in the cultured cells.These suggest that NA-evoked ATP-release is closely associated with Ca^<2+> mobilization in both endothelial and smooth muscle cells.Studies on the mechanisms of ATP and Nitric oxide :In the rat caudal arteries, bradykinin (BK) produced endothelium-dependent and L-NAME-sensitive relaxation, but did not evoke the release of ATP.BK clearly raised intracellular Ca^<2+> levels in the endothelial and smooth muscle cells of the caudal artery. Also, in the cultured cells, BK clearly raised intracellular Ca^<2+> levels, but did not evoke the release of ATP.These results suggest BK-evoked NO-release is closely associated with Ca^<2+> mobilization in endothelial cells alone and BK receptor does not couple with the mechanisms of ATP-release.From the present results, there may be no linkage between the mechanisms of ATP-release coupled with alpha_1-adrenoceptor and NO-release coupled with BK-receptor, although both releases are closely associated with Ca^<2+>. As one possibility, it is suggested that intracellular Ca^<2+> mobilization in smooth muscle cells may be involved in the release of ATP from endothelial cells and gap junctionbetween smooth muscle, and endothelial cells may play an important roles. Less

ATP释放机制的药理学研究：在大鼠尾动脉，去甲肾上腺素（NA）引起ATP及其代谢产物的释放，哌唑嗪、去钙和摩擦内皮可阻断NA引起的ATP及其代谢产物释放。钠钾交换液可促进ATP的释放。而40 mMKCl溶液和高渗溶液则抑制ATP的释放，因此去极化可能促进ATP的释放。缝隙连接抑制剂L-庚醇可抑制ATP的释放，提示ATP释放的机制与Ca^<2+>内流和缝隙连接密切相关，并呈电压依赖性. ATP释放机制的显微镜观察：在大鼠尾动脉，NA明显升高内皮细胞和平滑肌细胞内Ca^<2+>水平.另一方面，在从大鼠尾动脉分离的培养的内皮细胞中，NA不表达。 ...更多信息 不能升高细胞内Ca^<2+>水平。此外，NA并不引起培养细胞中ATP的释放，这表明NA引起的ATP释放与内皮细胞和平滑肌细胞中Ca^2+的动员密切相关。ATP和一氧化氮机制的研究：在大鼠尾动脉中，缓激肽（BK）产生内皮依赖性和L-NAME敏感性舒张，但不引起ATP的释放。BK明显升高尾动脉内皮细胞和平滑肌细胞中的细胞内Ca^2+水平。此外，在培养的内皮细胞中，BK明显升高细胞内Ca^<2+>水平，但不引起ATP的释放。这些结果表明，BK诱导的NO释放与内皮细胞中单独的Ca^<2+>动员密切相关，BK受体与ATP释放机制不偶联。从目前的结果来看，ATP释放与α_1-肾上腺素受体偶联的机制和NO释放与BK受体偶联的机制之间可能没有联系，尽管这两种释放都与Ca^<2+>密切相关。作为一种可能性，平滑肌细胞内Ca^2+动员可能参与了内皮细胞释放ATP和平滑肌间缝隙连接的过程，内皮细胞可能在其中起重要作用。少

项目成果

Kawamoto Y., Shinozuka K., Kunitomo M., Haginaka I.: "Determination of ATP and its metabolites released from rat caudal artery by isocratic ion-pair reversed-phase high-performance liquid chromatography" Analytical Biochemistry. 262 (1). 33-38 (1998)

Kawamoto Y.、Shinozuka K.、Kunitomo M.、Haginaka I.：“通过等度离子对反相高效液相色谱测定大鼠尾动脉释放的 ATP 及其代谢物”分析生物化学。

Tong,Y.C.et al.: "Evidence of ATP release from nerve and P2x-purinoceptor mediated contraction druing electrical stimulation of rat urinary bladder smooth muscle" Journal of Urology. 158. 1973-1977 (1997)

Tong,Y.C.等人：“电刺激大鼠膀胱平滑肌时神经和 P2x-嘌呤受体介导的收缩中 ATP 释放的证据”泌尿学杂志。

Shinozuka K.et al.: "Possible participation of ATP in changes of the blood pressure of SHR and old rats" Japanese Heart Journal. 39(4). 535-537 (1998)

Shinozuka K.et al.：“ATP 在 SHR 和老年大鼠血压变化中的可能参与”日本心脏杂志。

〓wamoto Y.et al.: "Determination of ATP and its metabolites released from rat caudal artery by isocratic ion-pair reverse-phase HPLC" Analytical Biochemistry. 262(1). 33-38 (1998)

〓wamoto Y. 等人：“通过等度离子对反相 HPLC 测定大鼠尾动脉释放的 ATP 及其代谢物”，Analytical Biochemistry 262(1)。

Shinozuka K.et al.: "Possible participation of ATP in changes of the blood pressure of SHR and old rats." Japanese Heart Journal. (in press). (1998)

Shinozuka K.et al.：“ATP 可能参与 SHR 和老年大鼠血压的变化。”