Glucagon-like peptide 1 modulates calcium responses to glutamate and membrane depolarization in hippocampal neurons

被引:99
作者
Gilman, CP
Perry, T
Furukawa, K
Grieg, NH
Egan, JM
Mattson, MP
机构
[1] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA
[2] NIA, Clin Invest Lab, Intramural Res Program, Baltimore, MD 21224 USA
[3] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA
关键词
calcium channels; cyclic AMP; cyclic AMP response element-binding protein; diabetes; excitotoxicity; synaptic plasticity;
D O I
10.1046/j.1471-4159.2003.02073.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Glucagon-like peptide 1 (GLP-1) activates receptors coupled to cAMP production and calcium influx in pancreatic cells, resulting in enhanced glucose sensitivity and insulin secretion. Despite evidence that the GLP-1 receptor is present and active in neurons, little is known of the roles of GLP-1 in neuronal physiology. As GLP-1 modulates calcium homeostasis in pancreatic beta cells, and because calcium plays important roles in neuronal plasticity and neurodegenerative processes, we examined the effects of GLP-1 on calcium regulation in cultured rat hippocampal neurons. When neurons were pre-treated with GLP-1, calcium responses to glutamate and membrane depolarization were attenuated. Whole-cell patch clamp analyses showed that glutamate-induced currents and currents through voltage-dependent calcium channels were significantly decreased in neurons pre-treated with GLP-1. Pre-treatment of neurons with GLP-1 significantly decreased their vulnerability to death induced by glutamate. Acute application of GLP-1 resulted in a transient elevation of intracellular calcium levels, consistent with the established effects of GLP-1 on cAMP production and activation of cAMP response element-binding protein. Collectively, our findings suggest that, by modulating calcium responses to glutamate and membrane depolarization, GLP-1 may play important roles in regulating neuronal plasticity and cell survival.
引用
收藏
页码:1137 / 1144
页数:8
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