肾上腺髓质素降低培养海马神经元胞内游离钙离子浓度(英文)

Adrenomedullin reduces intracellular calcium concentration in cultured hippocampal neurons

经荧光探针Fluo 3-AM标记细胞内游离钙后,用激光共聚焦显微镜检测肾上腺髓质素(adrenomedullin,ADM)对原代培养大鼠海马神经元内游离钙浓度([Ca2+]i)的影响.实验结果如下:(1)ADM(0.01～1.0μmol/L)浓度依赖性地降低细胞内钙浓度.(2)降钙素基因相关肽受体阻断剂(calcitonin gene-related peptide,CGRP8-37)预处理可部分抑制ADM的效应.(3)ADM可显著抑制高钾引起的[Ca2+]i增加.(4)ADM可显著抑制三磷酸肌醇(inositol 1,4,5-trisphosphate,IP3)引起的内钙释放,而对兰尼定(ryanodine)引起的内钙释放无显著影响.以上结果提示,ADM降低培养海马神经元内游离钙浓度,此作用与其抑制IP3引起的内钙释放有关,ADM对静息状态下的Ca2+内流无影响,但可显著抑制高钾引起的Ca2+内流,CGRP受体介导了ADM的上述效应.

The effects of adrenomedullin (ADM) on intracellular calcium concentration ([Ca2+]i) were investigated in cultured hippoc-ampal neurons. Changes in [Ca2+]i were detected by laser scanning confocal microscopy using Fluo 3-AM as the calcium fluorescentprobe. [Ca2+]i was represented by relative fluorescent intensity. The results showed that: (1) ADM (0.01~1.0 μmol/L) decreased theresting [Ca2+]i in a concentration-dependent manner. (2) Calcitonin gene-related peptide receptor antagonist CGRP8-37 significantlyinhibited the effects of ADM. (3) ADM significantly reduced the increase in [Ca2+]i induced by high K+. (4) ADM markedly inhibitedthe inositol 1,4,5-trisphosphate (IP3)-induced increase in [Ca2+]i, while did not influence ryanodine-evoked increase in [Ca2+]i. Theseresults suggest that ADM reduces [Ca2+]i in cultured hippocampal neurons through suppressing Ca2+ release from IP3-sensitive stores.Although ADM does not alter resting Ca2+ influx, it significantly suppresses Ca2+ influx activated by high K+. These effects may bepartly mediated by CGRP receptors. ADM in the CNS may act as a cytoprotective factor in ischemic/hypoxic conditions.