Prostaglandin E(2) stimulates glutamate receptor-dependent astrocyte neuromodulation in cultured hippocampal cells.
Recent Ca(2+) imaging studies in cell culture and in situ have shown that Ca(2+) elevations in astrocytes stimulate glutamate release and increase neuronal Ca(2+) levels, and that this astrocyte-neuron signaling can be stimulated by prostaglandin E(2) (PGE(2)). We investigated the electrophysiological consequences of the PGE(2)-mediated astrocyte-neuron signaling using whole-cell recordings on cultured rat hippocampal cells. Focal application of PGE(2) to astrocytes evoked a Ca(2+) elevation in the stimulated cell by mobilizing internal Ca(2+) stores, which further propagated as a Ca(2+) wave to neighboring astrocytes. Whole-cell recordings from neurons revealed that PGE(2) evoked a slow inward current in neurons adjacent to astrocytes. This neuronal response required the presence of an astrocyte Ca(2+) wave and was mediated through both N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors. Taken together with previous studies, these data demonstrate that PGE(2)-evoked Ca(2+) elevations in astrocyte cause the release of glutamate which activates neuronal ionotropic receptors.
Sanzgiri
R P
RP
Laboratory of Cellular Signaling, Department of Zoology and Genetics, Iowa State University, Ames, Iowa 50011, USA.
Araque
A
A
Haydon
P G
PG
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D001565:Benzoates / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology*; D008564:Membrane Potentials / Q000187:drug effects; D015213:Neuroimmunomodulation / Q000276:immunology*; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000276:immunology; D016194:Receptors, N-Methyl-D-Aspartate / Q000276:immunology*; D019284:Thapsigargin / Q000494:pharmacology
D001565:Benzoates; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C079694:alpha-methyl-4-carboxyphenylglycine; D019284:Thapsigargin; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D015232:Dinoprostone; D002118:Calcium; D005998:Glycine