Distribution of myo‐Inositol in the Cat Cochlear Nucleus

myo-Inositol plays a key role in signal transduction and osmotic regulation events in the CNS. Despite the known high concentrations of inositol in the human CNS, relatively little is known about its distribution within the different cell types. In this report, inositol homeostasis was studied in NT2-N cells, a unique cell culture model of human CNS neurons. Differentiation of precursor NT2 teratocarcinoma cells into NT2-N neurons by means of retinoic acid treatment resulted in an increase in inositol concentration from 24 to 195 nmol/mg of protein. After measurement of intracellular water spaces, inositol concentrations of 1.6 and 17.4 mM were calculated for NT2 and NT2-N cells, respectively. The high concentrations of inositol in NT2-N neurons could be explained by (1) an increased uptake of inositol (3.7 vs. 1.6 nmol/mg of protein/h, for NT2-N and NT2 cells, respectively) and (2) a decreased efflux of inositol (1.7%/h for NT2-N neurons vs. 9.0%/h for NT2 cells). Activity of inositol synthase, which mediates de novo synthesis of inositol, was not detected in either cell type. The observation that CNS neurons maintain a high intracellular concentration of inositol may be relevant to the regulation of both phosphoinositide signaling and osmotic stress events in the CNS.

Section: Discussionsupporting

confidence: 87%

Differentiated Human NT2‐N Neurons Possess a High Intracellular Content of myo‐Inositol

Novak

Turner

Agranoff

et al. 1999

“…However, inositol concentrations in some neuronal populations may equal or exceed those observed for glia. Concentrations of inositol approaching 10–20 m m have been reported for the Purkinje cell layer of the cat cerebellar flocculus (Godfrey et al . 1982), and for the giant neurons of Deiter's nucleus in the rabbit (Sherman et al .…”

Section: Distribution Of Inositol In Cns and Other Neural Tissuesmentioning

confidence: 88%

Inositol and higher inositol phosphates in neural tissues: homeostasis, metabolism and functional significance

Fisher

Novak

Agranoff

2002

357

306

Inositol phospholipids and inositol phosphates mediate wellestablished functions in signal transduction and in Ca 2+ homeostasis in the CNS and non-neural tissues. More recently, there has been renewed interest in other roles that both myo-inositol and its highly phosphorylated forms may play in neural function. We review evidence that myo-inositol serves as a clinically relevant osmolyte in the CNS, and that its hexakisphosphate and pyrophosphorylated derivatives may play roles in such diverse cellular functions as DNA repair, nuclear RNA export and synaptic membrane trafficking.

“…At a more microregional level brain shows large differences in myo-inositol concentration, inositol that is thought to be intracellular. For example, rabbit cerebellar molecular and medullary layers have myoinositol levels of 70.6 and 28.2 mmol/kg dry weight (Stewart et al, 1969); rat medial preoptic and lateral preoptic hypothalamic nuclei myo-inositol levels are 50.6 and 23.7 mmol/kg dry weight, on average (Sherman et al, 1977a), and cat cochlear nucleus has been found to have myo-inositol levels as high as 120 and as low as 12 mmol/kg dry weight in regions separated by a distance of only 2 mm (Godfrey et al, 1982). Such a unique distribution of tissue levels may be the result of active processes that relate to the metabolic requirements of individual or groups of cells.…”

Section: Figmentioning

confidence: 99%

Immunohistochemical Staining and Enzyme Activity Measurements Show myo‐Inositol‐1‐Phosphate Synthase to Be Localized in the Vasculature of Brain

Wong

Kalmbach

Hartman

et al. 1987

Self Cite

Rabbit anti-bovine myo-inositol-1-phosphate synthase was used to examine the distribution of that enzyme in perfused and immersion-fixed bovine brain and testis. In brain, intense and specific staining was found in the walls of all the vascular elements including cerebral capillaries. The remainder of brain parenchyma exhibited only low levels of background staining. In testis, an organ rich in the enzyme, blood vessels showed no specific staining. Instead, the enzyme was found in the seminiferous epithelium of the seminiferous tubules, perhaps localized in spermatozoa. To confirm the brain finding, the activity of myo-inositol-1-phosphate synthase was measured in bovine brain microvessel preparations and brain pial vessels. In these preparations the activity of the enzyme was found on average to be 7 and 22 times enriched over that in whole brain, respectively. The activities of two other enzymes of inositol metabolism, myo-inosose reductase and myo-inositol-1-phosphatase, were also examined for their distribution in brain. Those enzymes were found to be generally distributed. The surprising finding of a vascular localization of myo-inositol-1-phosphate synthase in brain raises new questions about the mechanism by which myo-inositol is concentrated to such high cellular levels in the principal substance of that organ.