Glucagon-like peptide 1 modulates calcium responses to glutamate and membrane depolarization in hippocampal neurons.
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.
Gilman
Charles P
CP
Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.
Perry
TracyAnn
T
Furukawa
Katsotoshi
K
Grieg
Nigel H
NH
Egan
Josephine M
JM
Mattson
Mark P
MP
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D005934:Glucagon / Q000378:metabolism* / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1; D018698:Glutamic Acid / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology; D009498:Neurotoxins / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D011498:Protein Precursors / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D015220:Calcium Channels; D018696:Neuroprotective Agents; D009498:Neurotoxins; D010446:Peptide Fragments; D011498:Protein Precursors; D018698:Glutamic Acid; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D002118:Calcium