肾上腺髓质素降低培养海马神经元胞内游离钙离子浓度
季淑梅, 薛建梅, 王川, 苏素文, 何瑞荣
燕山大学生物医学工程系. 河北, 秦皇岛 066004;河北医科大学, 药理室, 生理室. 河北, 石家庄 050017
摘要
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([Ca~(2+)]_(i))的影响.实验结果如下:ADM(0.01~1.0μmol/L)浓度依赖性地降低细胞内钙浓度。降钙素基因相关肽受体阻断剂(calcitonin gene-related peptide,CGRP_(8-37))预处理可部分抑制ADM的效应。ADM可显著抑制高钾引起的[Ca~(2+)]_(i)增加。ADM可显著抑制三磷酸肌醇(inositol 1,4,5-trisphosphate,IP_(3))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IP_(3)引起的内钙释放有关,ADM对静息状态下的Ca~(2+)内流无影响,但可显著抑制高钾引起的Ca~(2+)内流,CGRP受体介导了ADM的上述效应。
关键词: 肾上腺髓质素; 海马神经元; 细胞内钙; 降钙素基因相关肽受体阻断剂CGRP8-37; 三磷酸肌醇; 兰尼定; 激光共聚焦显微镜
Adrenomedullin reduces intracellular calcium concentration in cultured hippocampal neurons
Ji Shumei, Xue Jianmei, Wang Chuan, Su Suwen, He Ruirong
Department of Biomedical Engineering, Yanshan University. Qinhuangdao 066004, Hebei, China;Departments of Pharmacology and Physiology, Hebei Medical University. Shijiazhuang 050017, Hebei, China
Abstract
The effects of adrenomedullin (ADM) on intracellular calcium concentration ([Ca~(2+)]_(i)) were investigated in cultured hippocampal neurons. Changes in [Ca~(2+)]_(i) were detected by laser scanning confocal microscopy using Fluo 3-AM as the calcium fluorescent probe. [Ca~(2+)]_(i) was represented by relative fluorescent intensity. The results showed that: ADM (0.01~1.0 #mu#mol/L) decreased the resting [Ca~(2+)]_(i) in a concentration-dependent manner. Calcitonin gene-related peptide receptor antagonist CGRP_(8-37) significantly inhibited the effects of ADM. ADM significantly reduced the increase in [Ca~(2+)]_(i) induced by high K~(+). ADM markedly inhibited the inositol 1,4,5-trisphosphate (IP_(3))-induced increase in [Ca~(2+)]_(i), while did not influence ryanodine-evoked increase in [Ca~(2+)]_(i). These results suggest that ADM reduces [Ca~(2+)]_(i) in cultured hippocampal neurons through suppressing Ca~(2+) release from IP3-sensitive stores. Although ADM does not alter resting Ca~(2+) influx, it significantly suppresses Ca~(2+) influx activated by high K~(+). These effects may be partly mediated by CGRP receptors. ADM in the CNS may act as a cytoprotective factor in ischemic/hypoxic conditions.
Key words: Adrenomedullin;Hippocampal neurons;Intracellular calcium;Calcitonin gene-related peptide receptor antagonist (CGRP_(8-37));Inositol 1,4,5-trisphosphate;Ryanodine;Laser scanning confocal microscopy
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引用本文:
季淑梅, 薛建梅, 王川, 苏素文, 何瑞荣. 肾上腺髓质素降低培养海马神经元胞内游离钙离子浓度[J]. 生理学报 2005; 57 (3): .
Ji Shumei, Xue Jianmei, Wang Chuan, Su Suwen, He Ruirong. Adrenomedullin reduces intracellular calcium concentration in cultured hippocampal neurons. Acta Physiol Sin 2005; 57 (3): (in Chinese with English abstract).