Group I metabotropic glutamate receptors mediate the inhibition of phosphatidylserine synthesis in rat cerebellar slices: a possible role in physiology and pathology.
In cerebellar slices, the lowering of oxygen availability, obtained by bubbling N(2) in the medium, reduced the incorporation of radioactive serine into phosphatidylserine (PtdSer). CPCCOEt, an antagonist of metabotropic glutamate receptors type 1 (mGluR1) counteracted the effect, whereas antagonists of NMDA or AMPA receptors were ineffective. In oxygenated slices, agonists of Group I mGluRs, which include mGluR1, inhibited PtdSer synthesis. This effect was also counteracted by CPCCOEt. These findings indicate that glutamate inhibits PtdSer synthesis by acting on mGluR1. This could be important in relation to the known release of glutamate in hypoxia-ischaemia conditions. In cerebellar Purkinje cells, mGluR1 are involved in the generation of mGluR-EPSP evoked by parallel fibre stimulation. The administration of l-serine to cerebellar slices reduced in a dose-dependent manner the mGluR-EPSP evoked by parallel fibre stimulation. The effect was mostly due to the increased synthesis of PtdSer. Thus inhibition of PtdSer synthesis, mediated by mGluR1, may participate in the generation of mGluR-EPSP.
Buratta
Sandra
S
Department of Internal Medicine, Section of Biochemistry, University of Perugia, Perugia, Italy.
Mambrini
Raffaela
R
Miniaci
Maria Concetta
MC
Tempia
Filippo
F
Mozzi
Rita
R
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D015687:Cell Hypoxia / Q000502:physiology; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D004558:Electric Stimulation; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D010718:Phosphatidylserines / Q000096:biosynthesis*; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D012694:Serine / Q000378:metabolism / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D010718:Phosphatidylserines; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D012694:Serine