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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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Citing This Article：

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).