title: Potentiation of glutamatergic agonist-induced inositol phosphate formation by basic fibroblast growth factor is related to developmental features in hippocampal cultures: neuronal survival and glial cell proliferation.
abstract: We investigated the modulation by growth factors of phospholipase C (PLC)-linked glutamate receptors during in vitro development of hippocampal cultures. In defined medium, glial cells represent between 3 and 14% of total cell number. When we added basic fibroblast growth factor (bFGF) 2 h after plating, we found: (i) a neuroprotection from naturally occurring death for up to 5 days; (ii) a proliferation of glial cells from day 3; and (iii) a potentiation of quisqualate (QA)-induced inositol phosphate (IP) formation from 1 to 10 days in vitro (DIV) and 1S, 3R-amino-cyclopentane-1,3-dicarboxylate (ACPD) response from 3 to 10 DIV. The antimitotic cytosine-beta,D-arabinofuranoside (AraC) blocked glial cell proliferation induced by bFGF, but not neuroprotection. Under these conditions, the early potentiation of the QA response (1-3 DIV) was not changed, while the ACPD and late QA response potentiations were prevented (5-10 DIV). Epidermal growth factor was not neuroprotective but it induced both glial cell proliferation and late QA or ACPD potentiation. Surprisingly, the early bFGF-potentiated QA-induced IP response was blocked by 6, 7-dinitro-quinoxaline-2,3-dione (DNQX), suggesting the participation of ionotropic (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate (KA) receptors. The delayed bFGF-potentiated ACPD-induced IP response is inhibited by (S)-alpha-methyl-4-carboxyphenylglycine (MCPG), indicating possible activation of glial metabotropic receptors. These results suggest that, in hippocampal cultures, bFGF modulates AMPA and metabotropic glutamate receptors linked to the IP cascade, possibly in relation to the regulation of neuronal survival and glial cell proliferation, respectively.
authors.affiliation: Laboratoire de Plasticité Cérébrale, CNRS EP628, Université Montpellier II, France.
authors.forename: E M
authors.initials: EM
authors.lastname: Blanc
authors.forename: M
authors.initials: M
authors.lastname: Jallageas
authors.forename: M
authors.initials: M
authors.lastname: Recasens
authors.forename: J
authors.initials: J
authors.lastname: Guiramand
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D003561:Cytarabine / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005333:Fetus / Q000166:cytology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D018698:Glutamic Acid / Q000502:physiology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology; D007295:Inositol Phosphates / Q000096:biosynthesis*; D009457:Neuroglia / Q000166:cytology*; D009474:Neurons / Q000737:chemistry / Q000166:cytology* / Q000201:enzymology; D018696:Neuroprotective Agents / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D018091:Receptors, AMPA / Q000502:physiology*; D018092:Kainic Acid Receptors / Q000502:physiology; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D000964:Antimetabolites, Antineoplastic; D001565:Benzoates; D003515:Cycloleucine; D003561:Cytarabine; D004815:Epidermal Growth Factor; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D016222:Fibroblast Growth Factor 2; D018698:Glutamic Acid; D005998:Glycine; D007295:Inositol Phosphates; D018696:Neuroprotective Agents; D011810:Quinoxalines; D016318:Quisqualic Acid; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D010738:Type C Phospholipases; C036361:1-amino-1,3-dicarboxycyclopentane; C079694:alpha-methyl-4-carboxyphenylglycine; C056723:FG 9041