title: Astroglial phosphoinositide hydrolysis during combined glucose-oxygen deprivation: role of the metabotropic glutamate receptor.
abstract: Phosphatidylinositol bisphosphate hydrolysis, leading to the production of myo-inositol trisphosphate and diacylglycerol, may play a significant role in the pathogenesis of hypoxic-ischemic brain injury. We used tritiated myo-inositol phosphate (3H-IP) accumulation as a means to quantitate phosphoinositide hydrolysis in pre-labeled astroglial cultures subjected to combined glucose-oxygen deprivation. Astroglial cultures exposed to combined glucose-oxygen deprivation had significantly greater 3H-IP accumulation compared with cultures exposed to control conditions. To delineate the role of the metabotropic glutamate receptor in astroglial phosphoinositide hydrolysis during combined glucose-oxygen deprivation, we studied the effects of two metabotropic glutamate receptor antagonists, 2-amino-3-phosphonopropionic acid and (+)-methyl-4-carboxyphenylglycine. 2-Amino-3-phosphonopropionic acid attenuated the accumulation of 3H-IP during combined glucose-oxygen deprivation but acted as an agonist under control conditions. (+)-Methyl-4-carboxyphenylglycine had no effect on 3H-IP accumulation during combined glucose-oxygen deprivation or under control conditions. These results suggest that activation of astroglial phosphoinositide hydrolysis during combined glucose-oxygen deprivation may be mediated, at least in part, by the metabotropic glutamate receptor.
authors.affiliation: Wexner Institute for Pediatric Research, Children's Hospital, Columbus, Ohio, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Segeleon
authors.forename: D C
authors.initials: DC
authors.lastname: Lipscomb
authors.forename: S E
authors.initials: SE
authors.lastname: Haun
authors.forename: V L
authors.initials: VL
authors.lastname: Trapp
authors.forename: L A
authors.initials: LA
authors.lastname: Horrocks
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism*; D001565:Benzoates / Q000494:pharmacology; D002478:Cells, Cultured; D005947:Glucose / Q000008:administration & dosage*; D018698:Glutamic Acid / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006868:Hydrolysis; D007295:Inositol Phosphates / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D018021:Lithium Chloride / Q000494:pharmacology; D010100:Oxygen / Q000008:administration & dosage*; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000502:physiology*; D014316:Tritium
chemical_list: D001565:Benzoates; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D018094:Receptors, Metabotropic Glutamate; C000211:2-amino-3-phosphonopropionic acid; D014316:Tritium; C079694:alpha-methyl-4-carboxyphenylglycine; D018698:Glutamic Acid; D007770:L-Lactate Dehydrogenase; D018021:Lithium Chloride; D005947:Glucose; D000409:Alanine; D010100:Oxygen; D005998:Glycine