title: Profile of phosphatidylinositol metabolism stimulated by carbachol and glutamate in primary cultures of rat cerebellar neurons.
abstract: The formation of inositol phosphates, after stimulation of primary cultures of cerebellar neurons of the neonatal rat, in the presence of lithium chloride, by glutamate, carbachol, norepinephrine, histamine and Mg2+-free conditions, was measured by anion exchange high-pressure liquid chromatography (HPLC) with on-line radioactivity detection. All of the above agents caused a persistent, dose-dependent and calcium-sensitive preferential accumulation of inositol-4-phosphate, while the levels of inositol-1-phosphate were virtually unaffected. Agonist stimulation produced also a transient increase of a second peak which co-eluted with the standard for inositol 1,4-bisphosphate. However, no significant accumulation of inositol-1,4,5-trisphosphate and inositol-1,3,4,5-tetrakisphosphate was detected, possibly due to the fast kinetics of the metabolism of inositol phosphate. The results indicate that receptor-stimulated metabolism of inositol phosphate, in cultures of cerebellar granule cells, is due to a preferential hydrolysis of polyphosphoinositides and leads to the formation of inositol-4-phosphate through several calcium- and lithium-sensitive enzymatic steps.
authors.affiliation: Fidia-Georgetown Institute for the Neurosciences, Georgetown University School of Medicine, Washington, D.C. 20007.
authors.forename: S
authors.initials: S
authors.lastname: Hynie
authors.forename: J T
authors.initials: JT
authors.lastname: Wroblewski
authors.forename: E
authors.initials: E
authors.lastname: Costa
mesh_terms: D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005971:Glutamates / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology; D006868:Hydrolysis; D007295:Inositol Phosphates / Q000032:analysis; D008274:Magnesium / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D005971:Glutamates; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D006632:Histamine; D002217:Carbachol; D008274:Magnesium; D009638:Norepinephrine