title: Developmental and regional studies of the metabolism of inositol 1,4,5-trisphosphate in rat brain.
abstract: Coupling of CNS receptors to phosphoinositide turnover has previously been found to vary with both age and brain region. To determine whether the metabolism of the second messenger inositol 1,4,5-trisphosphate also displays such variations, activities of inositol 1,4,5-trisphosphate 5'-phosphatase and 3'-kinase were measured in developing rat cerebral cortex and adult rat brain regions. The 5'-phosphatase activity was relatively high at birth (approximately 50% of adult values) and increased to adult levels by 2 weeks postnatal. In contrast, the 3'-kinase activity was low at birth and reached approximately 50% of adult levels by 2 weeks postnatal. In the adult rat, activities of the 3'-kinase were comparable in the cerebral cortex, hippocampus, and cerebellum, whereas much lower activities were found in hypothalamus and pons/medulla. The 5'-phosphatase activities were similar in cerebral cortex, hippocampus, hypothalamus, and pons/medulla, whereas 5- to 10-fold higher activity was present in the cerebellum. The cerebellum is estimated to contain 50-60% of the total inositol 1,4,5-trisphosphate 5'-phosphatase activity present in whole adult rat brain. The localization of the enriched 5'-phosphatase activity within the cerebellum was examined. Application of a histochemical lead-trapping technique for phosphatase indicated a concentration of inositol 1,4,5-trisphosphate 5'-phosphatase activity in the cerebellar molecular layer. Further support for this conclusion was obtained from studies of Purkinje cell-deficient mutant mice, in which a marked decrement of cerebellar 5'-phosphatase was observed. These results suggest that the metabolic fate of inositol 1,4,5-trisphosphate depends on both brain region and stage of development.
authors.affiliation: Neuroscience Laboratory, University of Michigan, Ann Arbor 48104-1687.
authors.forename: A M
authors.initials: AM
authors.lastname: Heacock
authors.forename: E B
authors.initials: EB
authors.lastname: Seguin
authors.forename: B W
authors.initials: BW
authors.lastname: Agranoff
mesh_terms: D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D002531:Cerebellum / Q000201:enzymology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D009994:Osmolar Concentration; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
chemical_list: D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium