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Histamine potentiates IP3-mediated Ca2+ release via thapsigargin-sensitive Ca2+ pumps

机译:组胺通过毒胡萝卜素敏感的Ca2 +泵增强IP3介导的Ca2 +释放

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We have studied the histamine-induced potentiation of inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ release in HeLa cells. Intracellular IP3 levels were increased by IP3 dialysis with the whole-cell configuration of the patch-clamp technique (cell dialysis Of IP3) Low concentrations of extracellular histamine (I M) accelerated the rate Of IP3-mediated Ca2+ release, an effect that required the coincidence of both histamine signalling and the increase in IP3 levels. Our data suggest that the potentiation effect of histamine cannot be explained simply by agonist-induced increase in IP3 levels. Disordering microfilaments with cytochalasin D and microtubules with colchicine caused a decrease in the histamine-induced Ca2+ response. Furthermore, both cytochalasin D and colchicine diminished the rate of IP3-mediated Ca2+ release, while only the former reduced slightly the histamine-induced potentiation effect. Remarkably, rapid inhibition of SERCA pumps with thapsigargin to avoid the depletion of internal Ca2+ stores diminished the histamine-induced potentiation Of IP3-mediated Ca2+ release, without affecting the rate of IP3-mediated Ca2+ release. These data indicate that histamine-induced potentiation of Ca2+ release in HeLa cells requires active SERCA pumps and suggest that SERCA pumps are an important factor in determining the efficiency of agonist-induced Ca2+ release. (C) 2003 Elsevier Science Inc. All rights reserved. [References: 39]
机译:我们已经研究了组胺诱导的HeLa细胞中肌醇1,4,5-三磷酸(IP3)介导的Ca2 +释放的增强。通过膜片钳技术全细胞配置的IP3透析(IP3的细胞透析),通过IP3透析提高了细胞内IP3的水平。低浓度的细胞外组胺(IM)加快了IP3介导的Ca2 +释放的速率,这需要同时进行组胺信号转导和IP3水平的增加。我们的数据表明,组胺的增强作用不能简单地由激动剂诱导的IP3水平升高来解释。具有细胞松弛素D的微丝紊乱和具有秋水仙碱的微管紊乱导致组胺诱导的Ca2 +响应降低。此外,细胞松弛素D和秋水仙碱都降低了IP3介导的Ca2 +释放速率,而只有前者略微降低了组胺诱导的增强作用。值得注意的是,用毒胡萝卜素快速抑制SERCA泵以避免内部Ca2 +储存的消耗减少了组胺诱导的IP3介导的Ca2 +释放的增强,而不影响IP3介导的Ca2 +释放的速率。这些数据表明,在HeLa细胞中组胺诱导的Ca2 +释放增强需要激活SERCA泵,这表明SERCA泵是确定激动剂诱导的Ca2 +释放效率的重要因素。 (C)2003 Elsevier Science Inc.保留所有权利。 [参考:39]

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