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.

Maturational regulation of inositol 1,4,5-trisphosphate metabolism in rabbit airway smooth muscle.

“…Our present findings regarding the regulation of 3'-kinase activity are in agreement with recent studies using different cell types which reported that the activity of the enzyme is stimulated by physiological concentrations of Ca2 , with an optimal effect elicited at 10-6 M free Ca2+ concentration (22)(23)(24)(25). In this connection, we observed that maximal 3'-kinase activity was significantly increased in the presence of 10-6 M free Ca2+ in both the immature and adult TSM preparations (Fig.…”

“…The observed developmental change in 3'-kinase activity is similar to that reported in the maturing rat cerebral cortex, wherein 3'-kinase activity at two weeks ofage was also found to approximate 50% of the adult level (17,22). Moreover, as in the present study, the V. and Km values for 5'-phosphatase in the maturing rat brain were found to significantly exceed the corresponding 3'-kinase determinations (22).…”

“…Moreover, as in the present study, the V. and Km values for 5'-phosphatase in the maturing rat brain were found to significantly exceed the corresponding 3'-kinase determinations (22). On the other hand, our observed maturational decrease in 5'-phosphatase activity in rabbit TSM contrasts the reported developmental increase in the activity of the enzyme in rat brain (17,22), suggesting the presence of interspecies and/or tissue-specific differences in its developmental regulation.…”

Cloning and expression of human brain type I inositol 1,4,5‐trisphosphate 5‐phosphatase High levels of mRNA in cerebellar Purkinje cells

“…InsP3 5-phosphatase catalyzes the dephosphorylation of InsPa inactivating the signal. This enzyme is present at high concentration in the brain, particularly in the cerebellum [2,3]. Regulation of this enzyme will directly modify InsPa accumulation and Ca 2+ signalling.…”

Inositol 1,4,5-trisphosphate 3-kinases: functions and regulations

“…Rat IP3K activity is low at birth and reaches approximately 50% of adult levels [64]. Rat IP3K activities are the highest in the hippocampal CA1 pyramidal neurons, dentate gyrus granule cells, and cerebellar purkinje cells [64,65]. On the other hand, low activities were found in cerebellar granule cells, thalamus, hypothalamus, brainstem, spinal cord, and white matter tracts [64,65].…”