Ca2+ uptake, fatty acid, and LDH release during proximal tubule hypoxia: effects of mepacrine and dibucaine.
Ca2+ uptake, fatty acid, and LDH release during proximal tubule hypoxia: effects of mepacrine and dibucaine.
复制标题
近曲小管缺氧期间 Ca2 摄取、脂肪酸和 LDH 释放：美帕林和地布卡因的影响。
DOI：
10.1152/ajprenal.1994.266.2.f196
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Schrier,RW
中科院分区：
文献类型：
--
作者：
Bunnachak,D;Almeida,AR;Wetzels,JF;Gengaro,P;Nemenoff,RA;Burke,TJ;Schrier,RW
在新鲜分离的缺氧大鼠近端肾小管中，Ca2+ 摄取率在 1 分钟内迅速增加，并在整个 20 分钟缺氧期间保持显着升高。乳酸脱氢酶 (LDH) 释放是膜损伤的标志，仅在缺氧 5 分钟后增加，此后逐渐增加。通过用三种不同的磷脂酶抑制剂（即美帕林、地布卡因或对溴苯甲酰溴 (PBPB)）治疗缺氧肾小管，评估了增加 Ca2+ 摄取率激活磷脂酶的潜在影响，从而引发膜损伤。含氧量正常 10 分钟和 20 分钟后，LDH 释放平均分别为 11.9% 和 13.8%。缺氧 10 分钟或 20 分钟时，LDH 释放分别增加至 46.0 和 65.2%（P < 0.01），Ca2+ 摄取率从常氧条件下的 2.56 增加到缺氧 10 分钟时的 4.71 nmol.mg-1 x min-1（P < 0.01），从常氧条件下的 2.82 增加到缺氧 20 分钟时的 3.76 nmol/mg。缺氧分钟（P < 0.05）。在一系列单独的肾小管中，缺氧 10 分钟后，用 50 microM mepacrine（66.1 至 47.3%，P < 0.01）或 50 microM dibucaine（53.1 至 38.5%，P < 0.02）预处理减少了 LDH 释放。 Ca2+吸收率的增加也显着降低。缺氧 20 分钟后，mepacrine 和地布卡因均不会降低 Ca2+ 摄取率；地布卡因可适度减少 LDH 释放，但美帕林则不会。通过 LDH 释放评估，较高剂量的美帕林 (500 µM) 和地布卡因 (250 µM) 也可减少缺氧 10 分钟时的细胞损伤。（摘要截断为 250 字）
In freshly isolated hypoxic rat proximal tubules, Ca2+ uptake rate increases promptly, within 1 min, and remains significantly elevated throughout a 20-min period of hypoxia. Lactate dehydrogenase (LDH) release, a sign of membrane injury, increases only after 5 min of hypoxia and thereafter rises progressively. The potential effect of increased Ca2+ uptake rate to activate phospholipases, which would then initiate membrane injury, was evaluated by treating hypoxic tubules with three dissimilar phospholipase inhibitors, i.e., mepacrine, dibucaine, or p-bromophenacyl bromide (PBPB). LDH release averaged 11.9 and 13.8% after 10 and 20 min of normoxia, respectively. With 10 or 20 min of hypoxia LDH release increased to 46.0 and 65.2%, respectively (P < 0.01), and Ca2+ uptake rate increased from 2.56 in normoxia to 4.71 nmol.mg-1 x min-1 at 10 min of hypoxia (P < 0.01) and from 2.82 in normoxia to 3.76 nmol/mg at 20 min of hypoxia (P < 0.05). In a separate series of tubules, after 10 min of hypoxia LDH release was reduced by pretreatment with 50 microM mepacrine (66.1 to 47.3%, P < 0.01) or 50 microM dibucaine (53.1 to 38.5%, P < 0.02). The increase in Ca2+ uptake rate also was significantly reduced. After 20 min of hypoxia neither mepacrine nor dibucaine reduced Ca2+ uptake rate; LDH release was modestly reduced by dibucaine but not mepacrine. Higher doses of mepacrine (500 microM) and dibucaine (250 microM) also reduced cell injury at 10 min of hypoxia as assessed by LDH release.(ABSTRACT TRUNCATED AT 250 WORDS)