lithium-chloride and alpha-methyl-4-carboxyphenylglycine

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.

Topics: Alanine; Animals; Animals, Newborn; Astrocytes; Benzoates; Cells, Cultured; Glucose; Glutamic Acid; Glycine; Hydrolysis; Inositol Phosphates; L-Lactate Dehydrogenase; Lithium Chloride; Oxygen; Phosphatidylinositols; Rats; Rats, Sprague-Dawley; Receptors, Metabotropic Glutamate; Tritium