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Control of adrenal catecholamine secretion by Ca^<2+> storing mechanisms

Ca^2存储机制对肾上腺儿茶酚胺分泌的控制

基本信息

批准号：
06454121
负责人：
NAKAZATO Yoshikazu
金额：
$ 4.35万
依托单位：
HOKKAIDO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06454121/
关键词：
ATP Adrenal chromaffin cells Ca influx GTP analogues Catecholamine secretion Ca stores Na-Ca exhange Whole cell voltage clamp カルシウム電流シクロピアゾン酸細胞内カルシウム濃度モルモットカルシウムATPアーゼ

项目摘要

1. Catecholamine (CA) secretion depending on intracellular Ca store and the effect of extracellular Na : The effect of ryanodine and Ca-ATPase inhibitors on Ca releasing action of caffeine and muscarine from Ca stores was studied in perfused adrenal glands and dispersed chromaffin cells of the quinea pig. In the absence of extracellular Ca, both caffeine and muscarine caused only a small increase in CA secretion which was greatly enhanced after further removal of extracellular Na. Readmission of Ca during perfusion with Na-and Ca-free solution caused inhibition of CA secretion which was reversed to the augmentation by treatment with Ca-ATPase inhibitors.2. Kinetics of intracellular Ca depending on Ca store and ionic channel activation in single cells : Ryanodine blocked caffeine-induced increase in [Ca]i, but not that induced by muscarine. Inositol 1,4,5, trisphosphate (IP3) and thapsigargin increased[Ca]i and the latter evoked marked inward current. These results suggest that the depletion of intracellular Ca stores in adrenal chromaffin cells may faciliate Ca influx and thus CA secretion through some unknown mechanism as found in smooth muscle cells.3. Effect of ATP on Ca currents : The effect of ATP on membrane currents was investigated using whole cell voltage clamp techniques. ATP evoked inward current through non-selective cation channels and inhibited Ca currents evoked by depolarizing pulses. The inhibitory effect was abolished by dialysis with GTP analogues. These results suggest that ATP-induced increase in [Ca]i inhibits voltage dependent Ca influx through a mechanism coupled to G protein.

1. 儿茶酚胺（Catecholamine， CA）的分泌依赖于细胞内CA的储存和细胞外Na的影响：在豚鼠灌注肾上腺和分散染色质细胞中研究了ryanodine和CA - atp酶抑制剂对CA储存中咖啡因和肌碱释放CA的影响。在没有细胞外Ca的情况下，咖啡因和毒蕈碱都只引起Ca分泌的少量增加，在进一步去除细胞外Na后，Ca分泌大大增加。再灌注na -和Ca-free溶液时，Ca的分泌受到抑制，而Ca- atpase抑制剂的作用则相反。细胞内钙依赖于钙储存和单细胞离子通道激活的动力学：Ryanodine阻断了咖啡因诱导的[Ca]i的增加，但没有阻止毒蕈碱诱导的增加。肌醇1,4,5，三磷酸（IP3）和信号素增加[Ca]i，后者引起明显的内向电流。这些结果表明，肾上腺染色质细胞内钙储存的消耗可能促进钙内流，从而通过平滑肌细胞中发现的某种未知机制促进钙的分泌。ATP对钙电流的影响：利用全细胞电压箝位技术研究了ATP对膜电流的影响。ATP通过非选择性阳离子通道诱导向内电流，抑制去极化脉冲诱导的Ca电流。用GTP类似物透析可消除这种抑制作用。这些结果表明，atp诱导的[Ca]i增加通过与G蛋白偶联的机制抑制电压依赖性Ca内流。