1. Glucagon-like peptide 1 modulates calcium responses to glutamate and membrane depolarization in hippocampal neurons.
- Author
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Gilman CP, Perry T, Furukawa K, Grieg NH, Egan JM, and Mattson MP
- Subjects
- Animals, Calcium Channels drug effects, Calcium Channels metabolism, Cell Death drug effects, Cells, Cultured, Glucagon pharmacology, Glucagon-Like Peptide 1, Neurons cytology, Neurons drug effects, Neuroprotective Agents metabolism, Neuroprotective Agents pharmacology, Neurotoxins pharmacology, Patch-Clamp Techniques, Peptide Fragments pharmacology, Protein Precursors pharmacology, Rats, Rats, Sprague-Dawley, Calcium metabolism, Cell Membrane metabolism, Glucagon metabolism, Glutamic Acid pharmacology, Hippocampus cytology, Neurons physiology, Peptide Fragments metabolism, Protein Precursors metabolism
- Abstract
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.
- Published
- 2003
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