The deposition and metabolism of polyphosphoinositides in rat and guinea-pig brain during development

Abstract

1. The deposition of triphosphoinositide and diphosphoinositide in rat and guinea-pig cerebral hemispheres during growth was measured. 2. The maximum increase in concentration of both of these phospholipids occurs during the period of myelination, but in the rat some di- and tri-phosphoinositide is present before significant myelination begins. 3. In guinea-pig cerebral hemispheres the polyphosphoinositides remaining after post-mortem breakdown are selectively enriched in dissected white matter compared with grey matter. 4. The polyphosphoinositides in the cerebral hemispheres of rats were labelled with injected (32)P very rapidly; the specific radioactivities were in the order triphosphoinositide>diphosphoinositide>monophosphoinositide>total lipid phosphorus. 5. The synthesis of triphosphoinositide in rat forebrain occurs at an appreciable rate before, and at the start of, myelination, but the amount formed per gram of tissue is four to five times greater in adult rat brains, thus maintaining a constant turnover time (about 1hr.) for the whole triphosphoinositide fraction. This indicates that the rapid turnover of triphosphoinositide is independent of myelin deposition. 6. The specific radioactivity of the brain acid-soluble phosphorus pool referred to a constant dose of (32)P/g. body wt. falls rapidly with age, reaching a minimum at 13-14 days, and then rises again. The specific radioactivities of the polyphosphoinositides reflect this change. 7. Part of the polyphosphoinositides in rat and guinea-pig cerebral hemispheres is rapidly hydrolysed post mortem leaving a stable portion resistant to further breakdown. 8. The rate and extent of post-mortem hydrolysis of the polyphosphoinositides in both species decrease with age. 9. After (32)P labelling, the specific radioactivity of the triphosphoinositide remaining in the cerebral hemispheres of the rat after post-mortem breakdown is lower than the original triphosphoinositide fraction, suggesting two metabolically distinct pools.