Protein kinase C differently regulates quisqualate- and 1S,3R-trans aminocyclopentane dicarboxylate-induced phosphoinositide hydrolysis during in vitro development of hippocampal neurons.
Transient peaks of quisqualate (QA)-, but not 1S,3R-1-amino-3-cyclopentane dicarboxylate (1S,3R-ACPD)- and carbachol-induced inositol phosphate formation occur between 2 and 5 days in vitro (DIV) in hippocampal neurons in culture. In order to elucidate the putative origin of such developmental activity differences, the effect of PKC on metabotropic glutamate receptor (mGluR) and muscarinic receptor responses was investigated at 3 and 10 DIV. (i) Stimulation of PKC by phorbol-12,13-dibutyrate inhibited QA, 1S,3R-ACPD and carbachol responses at 3 DIV. At 10 DIV, only 1S,3R-ACPD response was still inhibited by phorbol esters. (ii) Inhibition of PKC by staurosporine at 3 DIV potentiated 1S,3R-ACPD-induced inositol phosphate formation, but had no effect on QA and carbachol responses. At 10 DIV, all responses were potentiated by staurosporine. These data strongly suggest that PKC differently modulates 1S,3R-ACPD- and QA-induced inositol phosphate accumulations during in vitro development. The specific activity of mGluRs during development, vs that of muscarinic receptor, and the peculiar modes of regulation by PKC of these two mGluR activities further suggest their particular involvement in the maturation of neuronal culture.
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INSERM U.254, Hôpital St Charles, Montpellier, France.
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D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006868:Hydrolysis; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins / Q000494:pharmacology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016318:Quisqualic Acid / Q000494:pharmacology*; D051381:Rats; D019311:Staurosporine
D000470:Alkaloids; D009498:Neurotoxins; D010716:Phosphatidylinositols; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D015240:Phorbol 12,13-Dibutyrate; D016318:Quisqualic Acid; D002217:Carbachol; D011493:Protein Kinase C; D019311:Staurosporine