Lysophosphatidic acid induces a sustained elevation of neuronal intracellular calcium.
Lysophosphatidic acid (LPA) is a lipid biomediator enriched in the brain. A novel LPA-induced response in rat hippocampal neurons is described herein, namely, a rapid and sustained elevation in the concentration of free intracellular calcium ([Ca2+]i). This increase is specific, in that the related lipids phosphatidic acid and lysophosphatidylcholine did not induce an alteration in [Ca2+]i. Moreover, consistent with a receptor-mediated process, there was no further increase in [Ca2+]i after a second addition of LPA. The LPA-induced increase in [Ca2+]i required extracellular calcium. However, studies with Cd2+, Ni2+, and nifedipine and nystatin-perforated patch clamp analyses did not indicate involvement of voltage-gated calcium channels in the LPA-induced response. In contrast, glutamate appears to have a significant role in the LPA-induced increase in [Ca2+]i, because this increase was inhibited by NMDA receptor antagonists and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate receptor antagonists. Thus, LPA treatment may result in an increased extracellular glutamate concentration that could stimulate AMPA/kainate receptors and thereby alleviate the Mg2+ block of the NMDA receptors and lead to glutamate stimulation of an influx of calcium via NMDA receptors.
Holtsberg
F W
FW
Molecular and Cell Biology Group, T. H. Morgan School of Biological Sciences, University of Kentucky, Lexington 40506-0225, U.S.A.
Steiner
M R
MR
Furukawa
K
K
Keller
J N
JN
Mattson
M P
MP
Steiner
S M
SM
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D015640:Ion Channel Gating / Q000502:physiology; D008246:Lysophospholipids / Q000494:pharmacology*; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
D015220:Calcium Channels; D018691:Excitatory Amino Acid Antagonists; D008246:Lysophospholipids; D011810:Quinoxalines; D017470:Receptors, Glutamate; D018698:Glutamic Acid; C056723:FG 9041; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C056639:2-amino-5-phosphopentanoic acid; D014633:Valine; D002118:Calcium