Myo-inositol transport in the central nervous system

Abstract

Free myo-inositol (inositol) transport into the cerebrospinal fluid (CSF), brain, and choroid plexus and out of the cerebrospinal fluid was measured in rabbits. In vivo, inositol transport from blood into choroid plexus, CSF, and brain was saturable with an apparent affinity constant (K-t) of approximately 0.1 mM. The relative turnover of free inositol in choroid plexus (16 percent/h) was higher than in CSF 4percent/h) and brain (0.3percent/h) when meausred by tissue penetration of tracer [3-H]-labeled inositol injected into blood. However, the passage of tracer inositol was not greater than the passage of mannitol into brain when measured 15 s after a rapid injection of inositol and mannitol into the left common carotid artery. From the CSF, the clearance of inositol relative to inulin was saturable after the intraventricular injection of various concentrations of inositol and inulin. Moreover, a portion of the inositol cleared from the CSF entered brain by a saturable mechanism. In vitro, choroid plexuses, isolated from rabbits and incubated in artificial CSF, accumulated [3-H-labeled myo-inositol against a concentration gradient by a specific, active, saturable process with a K-t of 0.2 mM inositol. These results were interpreted as showing that the entry of inositol into the central nervous system from blood is regulated by a saturable transport system, and that the locus of this system may be, in part, in the choroid plexus.

Identification of a Novel Na+/myo-Inositol Cotransporter

“…SMIT2, when expressed in oocytes, transports MI with a K m (120 M) closely corresponding to the 70 M human plasma concentration of MI (14) and well below the 470 M concentration reported for cerebrospinal fluid (37) and has a substantial I max that compares well with other sodium-coupled cotransporters. Furthermore, the K m for glucose is well above normal serum glucose levels.…”

Concentration of Myo-inositol in Skeletal Muscle of the Rat Occurs without Active Transport

“…Brain levels of MI, however, are more than 20 times that of cerebrospinal fluid. Nevertheless, active transport has not been demonstrable with brain slices (11) and isolated brain synaptosomes (13). The uptake of MI by synaptosomnes was not saturable and was not inhibited by dinitrophenol or ouabain.…”

“…The brain contains the highest known concentration of nonphosphorylated MI of any tissue in the body but its mechanism of concentration remains in dispute. The blood brain barrier prevents free access of plasma MI into brain but Spector and Lorenzo (11) and Spector (12) have clearly demonstrated that both MI and sciyllo-inositol are accumulated within the choroid plexus by a single, specific, energy-requiring transport process that depends on intracellular reduced sulfhydryl bonds. After its concentration in the choroid plexus, MI apparently enters cerebral spinal fluid by simple diffusion.…”

Phage-Displayed Recombinant Peptides for Non-Invasive Imaging Assessment of Tumor Responsiveness to Ionizing Radiation and Tyrosine Kinase Inhibitors

“…Millions of different single chain antibodies on phages are used for isolating highly specific therapeutic antibody leads. One of the most successful examples was adalimumab (Abbott Laboratories), the first fully human antibody targeted to TNF alpha (Spector and Lorenzo, 1975).…”