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PubMed2001

Abalone, Haliotis discus hannai Ino, can synthesize myo-inositol de novo to meet physiological needs.

The experiments were conducted to investigate the effects of dietary myo-inositol on the survival, growth, proximate composition and de novo synthesis of myo-inositol in abalone, Haliotis discus hannai Ino. The possible inositol-synthesizing capacity of intestinal microflora was also examined. Seven semipurified diets were formulated to provide graded levels of myo-inositol (28.7-1020.1 mg/kg diet). A control diet, the basal diet supplemented with 4 g/kg tetracycline hydrochloride, was employed to suppress synthesis of myo-inositol by intestinal bacteria. Abalone juveniles of similar size (weight, 144.6 +/- 0.8 mg; shell length, 10.92 +/- 0.10 mm) were distributed in a flow-through system using a completely randomized design with eight treatments and three replicates per treatment. They were fed the appropriate diets once daily for 16 wk. Survival, growth, crude protein, lipid, moisture of whole soft body and visceral inositol content were independent of myo-inositol supplementation (P > 0.05). The addition of the antibiotic also did not affect the survival, growth and whole soft body composition. It indicated that intestinal microflora contributed little to the myo-inositol nutrition in abalone. The present study, for the first time, demonstrated de novo synthesis of myo-inositol in mollusks because the visceral tissue of abalone showed high levels of myo-inositol synthetase activities (combined activities of myo-inositol-1-phosphate synthetase and inositol-1-phosphatase), ranging from 74.0 to 98.2 micromol/(h x g protein). The enzyme activity significantly and negatively correlated with dietary myo-inositol level (r = -0.81). Hence, dietary myo-inositol is not essential for abalone because tissue synthesis of the vitamin appears to be sufficient to support normal growth and health of this mollusk.

Animals↗
PubMed2003

High-affinity myo-inositol transport in Candida albicans: substrate specificity and pharmacology.

Inositol is considered a growth factor in yeast cells and it plays an important role in Candida as an essential precursor for phospholipomannan, a glycophosphatidylinositol (GPI)-anchored glycolipid on the cell surface of Candida which is involved in the pathogenicity of this opportunistic fungus and which binds to and stimulates human macrophages. In addition, inositol plays an essential role in the phosphatidylinositol signal transduction pathway, which controls many cell cycle events. Here, high-affinity myo-inositol uptake in Candida albicans has been characterized, with an apparent K(m) value of 240 +/- 15 microM, which appears to be active and energy-dependent as revealed by inhibition with azide and protonophores (FCCP, dinitrophenol). Candida myo-inositol transport was sodium-independent but proton-coupled with an apparent K(m) value of 11.0 +/- 1.1 nM for H(+), equal pH 7.96 +/- 0.05, suggesting that the C. albicans myo-inositol-H(+) transporter is fully activated at physiological pH. C. albicans inositol transport was not affected by cytochalasin B, phloretin or phlorizin, an inhibitor of mammalian sodium-dependent inositol transport. Furthermore, myo-inositol transport showed high substrate specificity for inositol and was not significantly affected by hexose or pentose sugars as competitors, despite their structural similarity. Transport kinetics in the presence of eight different inositol isomers as competitors revealed that proton bonds between the C-2, C-3 and C-4 hydroxyl groups of myo-inositol and the transporter protein play a critical role for substrate recognition and binding. It is concluded that C. albicans myo-inositol-H(+) transport differs kinetically and pharmacologically from the human sodium-dependent myo-inositol transport system and constitutes an attractive target for delivery of cytotoxic inositol analogues in this pathogenic fungus.

Azides↗
PubMed2006

Inositol deficiency diet and lithium effects.

OBJECTIVES: A major hypothesis explaining the therapeutic effect of lithium (Li) in mania is depletion of inositol via inhibition of inositol monophosphatase. However, inositol is also present in the diet. Restriction of dietary inositol could theoretically enhance the effects of Li. METHODS: We used dietary inositol restriction in animal studies and also devised a palatable diet for humans that is 90% free of inositol. RESULTS: Dietary inositol restriction significantly augmented the inositol-reducing effect of Li in rat frontal cortex. Li reduced inositol levels by 4.7%, inositol-deficient diet by 5.1%, and Li plus inositol-deficient diet by 10.8%. However, feeding with the inositol-deficient diet did not enhance the behavioral effect of Li in the Li-pilocarpine seizure model. Fifteen patients participated in an open clinical study of the inositol-deficient diet: six rapid cycling bipolar patients responding inadequately to Li or valproate in different phases of illness; two Li-treated bipolar outpatients with residual symptomatology, and seven inpatient Li-treated bipolar patients in non-responding acute mania. The diet had a major effect in reducing the severity of affective disorder in 10 of the patients within the first 7-14 days of treatment. CONCLUSION: These results suggest that dietary inositol restriction may be useful in some bipolar patients, but controlled replication is necessary.

Adult↗
PubMed2003

Kinetics of myo-inositol loading in women of reproductive age.

BACKGROUND: Myo-inositol plays a key role in an important intracellular signalling pathway. A deranged myo-inositol metabolism has been associated with neural tube defects. A myo-inositol loading test was performed to investigate the kinetics in healthy women of reproductive age. METHODS: Five healthy non-obese females [mean age (standard deviation: SD) 22.8 (2.2) years] were recruited at the University Medical Center Nijmegen. Blood samples were drawn fasting and at 20, 40, 60, 90, 180 and 270 min after ingestion of 100 mg/kg body weight of myo-inositol. Urine samples were collected before myo-inositol loading and at 180 and 270 min post-loading. Samples were analysed for serum myo-, epi- and scyllo-inositol and glucose concentrations by gas chromatography. Plasma insulin concentrations were determined by radio-immunoassay. Random intercept models were fitted to evaluate the data. RESULTS: The estimated myo-inositol and scyllo-inositol concentrations both reached maximum values at 180 min post-loading, respectively: mean (SD) 101.5 (9.2) micro mol/L and 1.09 (0.11) micro mol/L. The estimated plasma insulin and serum glucose concentrations decreased slightly but significantly during the experiment: P < 0.0001 and P < 0.05, respectively. At 180 and 270 min post-loading, urinary myo-inositol concentrations were increased and urinary glucose concentrations were unchanged. CONCLUSIONS: Myo-inositol enters the bloodstream quickly after oral ingestion and a small amount of myo-inositol is converted to scyllo-inositol. The synthesis of glucose from myo-inositol could not be detected by serum measurements. These data can be used in further research into the association between myo-inositol and neural tube defects.

Adult↗
PubMed1991

Role for ionotropic and metabotropic receptors in quisqualate-stimulated inositol polyphosphate accumulation in rat cerebral cortex.

The actions of the excitatory amino acid quisqualate (QA) on inositol polyphosphate accumulation in cerebral cortex slices have been assessed using both [3H]inositol prelabeling and mass measurements over relatively short incubation periods. QA stimulated accumulation of all the inositol polyphosphates, with similar EC50 values (2.8 +/- 0.7 microM). High performance liquid chromatography analysis of isomeric forms of inositol polyphosphates and specific mass assays revealed that both phosphorylation and dephosphorylation products of inositol-1,4,5-trisphosphate accumulate. A large component of the QA-stimulated inositol polyphosphate accumulation was inhibited by the ionotropic antagonist 6,7-dinitroquinoxaline-2,3-dione in a competitive manner. This implied that the QA response may be due to entry of Ca2+ via voltage-sensitive calcium channels as a consequence of an ionotropic receptor-induced depolarization. In support of this mechanism, the QA-induced response was dependent on the presence of extracellular calcium, whereas the well characterized muscarinic receptor agonist response to carbachol showed only a slight reduction under the same conditions. The concentration-dependent (EC50 8.8 +/- 3 microM) response to the selective ionotropic agonist amino-3-hydroxy-5-methyl-4-isoazolepropionic acid (AMPA) differed from that to QA or carbachol, in that accumulation of only [3H]inositol mono- and bisphosphates was stimulated, with no increase in the [3H]inositol tris- or tetrakisphosphates. Use of the metabotropic agonist (trans)-(+/-)-1-aminocyclopentyl-1,3-dicarboxylate (ACPD), however, produced concentration-dependent increases in all [3H]inositol polyphosphates. Although both AMPA and ACPD responses alone were smaller in magnitude than that to QA, when present together AMPA and ACPD produced additive responses on [3H]inositol mono- and bisphosphate and a marked synergistic increase in [3H]inositol tetrakisphosphate accumulation, resulting in a response similar to that seen for QA. These data suggest that QA-evoked responses in rat cortex slices are the result of a complex interaction mediated through both ionotropic and metabotropic receptors, in which Ca2+ entry may stimulate accumulation of inositol mono- and bisphosphate directly and divert the metabolism of inositol-1,4,5-trisphosphate to inositol-1,3,4,5-tetrakisphosphate.

Animals↗
PubMed1986

Quantitative changes in inositol 1,4,5-trisphosphate in chemoattractant-stimulated neutrophils.

myo-Inositol 1,4,5-trisphosphate is an intracellular second messenger generated from the hydrolysis of phosphatidylinositol 4,5-bisphosphate by phospholipase C. In the present study, we have used the abilities of inositol 1,4,5-trisphosphate to inhibit inositol 1,4,5-tris[32P]phosphate binding and to stimulate release of sequestered stores of 45Ca2+ to assay the mass of inositol 1,4,5-trisphosphate in extracts derived from [3H]inositol-prelabeled chemoattractant-stimulated neutrophils. These assays are specific for inositol 1,4,5-trisphosphate since the relative capacity of the extracts to compete with inositol 1,4,5-tris[32P]phosphate binding and to release 45Ca2+ correlated well with the [3H]inositol 1,4,5-trisphosphate content of the extract as determined by high pressure liquid chromatography. No correlation of these activities was observed with the content in the extract of either [3H]inositol 1,3,4-trisphosphate or [3H]inositol 1,3,4,5-tetrakisphosphate, whose formation exhibited kinetics distinct from [3H]inositol 1,4,5-trisphosphate. Thus, within 10 s of stimulation with 10 nM formyl-methionyl-leucyl-phenylalanine, the inositol 1,4,5-trisphosphate content of the extract increased from 0.05 to 0.55 pmol/10(6) cells, equivalent to a change in intracellular concentration from 100 nM to 1.1 microM. These studies demonstrate that neutrophils produce sufficient quantities of inositol 1,4,5-trisphosphate to mobilize Ca2+ from intracellular stores.

Animals↗
PubMed1986

Analysis of inositol mono- and polyphosphates by gas chromatography/mass spectrometry and fast atom bombardment.

The electron ionization spectra of all of the positional isomers of myo-inositol monophosphate and of myo-inositol 1,2-cyclic phosphate were obtained by gas chromatography/mass spectrometry of the pertrimethylsilyl derivatives. The fragmentation pattern of pertrimethylsilyl myo-inositol-1-phosphate was studied using deuterium labeling. The phosphate moiety was found to direct fragmentation to produce fragment ions of useful intensity with specific carbon retention. The spectrum of pertrimethylsilyl myo-inositol-1,4-bisphosphate is also described. An electron impact gas chromatographic/mass spectrometric method for myo-inositol-1-phosphate has been developed, which has a sensitivity to a level of 0.1 pmol. The positive and negative ion fast atom bombardment spectra of myo-inositol hexakis(disodium phosphate) and myo-inositol hexakis(dihydrogen phosphate) are described. The lesser-phosphorylated inositol polyphosphates were also studied, including inositol pentakis and inositol tetrakis(dihydrogen phosphates) as well as D-myo-inositol-1,4,5-trisphosphate and D-myo-inositol-1,4-bisphosphate from human red blood cells. The sensitivity of fast atom bombardment for the measurement of the latter two substances allows their detection to a level of about 10 nmol. The fast atom bombardment spectrum of synthetic myo-inositol 1,2-cyclic phosphate revealed variable amounts of a dimer produced during its preparation.

Electrons↗
PubMed1987

Identification of a novel inositol bisphosphate isomer formed in chemoattractant stimulated human polymorphonuclear leukocytes.

Analysis of inositol phosphate formation in chemoattractant-stimulated human polymorphonuclear leukocytes demonstrated the production of inositol 1,4,5-trisphosphate, inositol 1,3,4-trisphosphate, inositol 1,3,4,5-tetrakisphosphate, inositol 1,4-bisphosphate and another inositol bisphosphate isomer not detected in unstimulated cells. Studies in cell sonicates provided evidence that the previously unidentified inositol bisphosphate isomer is produced via the degradation of inositol 1,3,4-trisphosphate. This unidentified inositol bisphosphate peak was purified by high pressure liquid chromatography, and base hydrolyzed to form a mixture of inositol monophosphate isomers. Based on these studies, the unidentified peak was identified as inositol 3,4-bisphosphate. Identification of this isomer defines a new metabolic product derived from the initial inositol 1,4,5-trisphosphate formation, and also suggests another substrate for the inositol 1-phosphatase.

Calcium↗
PubMed1995

The norepinephrine-stimulated inositol phosphate response in human atria.

Inositol phosphate release and metabolism were studied in right atrial appendages obtained from 18 patients undergoing coronary artery bypass surgery and/or mitral valve replacement. [3H]Inositol-labeled human atria contained inositol(1,4. 5)trisphosphate, inositol(1,4)bisphosphate and the 1- (or 3) and 4-isomers of inositol monophosphate. Addition of norepinephrine (100 mumol/l) activated the release of inositol phosphates, as indicated by increased [3H]inositol label in all of these inositol phosphates. However, the phosphorylation product of inositol (1.4.5)trisphosphate, inositol-(1,3,4,5)tetrakisphosphate, and its metabolic products were not detected, either in control or stimulated atria. Similar inositol phosphate profiles were observed in rat right atria. Furthermore, both human and rat atria contained high concentrations of inositol(1,4,5)trisphosphate, which were not observed to increase with norepinephrine stimulation. The inositol phosphate responses to norepinephrine in rat and human cardiac tissue appear to be similar, except for the generally lower activity observed in human tissue. Thus, the rat provides a suitable model for the study of cardiac phosphatidylinositol turnover.

Adrenergic alpha-Agonists↗
PubMed1987

The effects of fatty acids on phosphoinositide synthesis and myo-inositol accumulation in exocrine pancreas.

The effects of arachidonic acid (20:4) on phosphoinositide turnover were examined in rat pancreatic acinar cells prelabeled with myo-[3H]inositol. Arachidonic acid (50 microM) increased the accumulation of myo-[3H]inositol, but not that of [3H]inositol monophosphate, [3H]inositol bisphosphate, or [3H]inositol trisphosphate. By contrast, 10 microM carbamoylcholine increased the accumulation of all four compounds. A combination of arachidonic acid plus carbamoylcholine caused a selective and marked accumulation of myo-[3H]inositol, which was abolished by 10 mM LiCl. Arachidonic acid (10-100 microM) produced a concentration-dependent inhibition of myo-[3H]inositol incorporation into phosphoinositides and markedly depressed carbamoylcholine-induced increases in myo-[3H]inositol incorporation into inositol phospholipids. Several other unsaturated and saturated fatty acids failed to elicit a synergistic response with carbamoylcholine in stimulating myo-[3H]inositol accumulation and did not retard the incorporation of myo-[3H]inositol into phosphoinositides. The fact that eicosapentaenoic acid (20:5), but not arachidic acid (20:0), mimicked the depressant effect of arachidonate on phosphoinositide labeling suggests that the degree of unsaturation of the fatty acid, rather than chain length, is important for inhibition of phosphoinositide synthesis. The arachidonate-induced decrease in myo-[3H]inositol incorporation was accompanied by a reduction in the steady state level of [32P]phosphatidylinositol 4,5-bisphosphate. The mass of arachidonic acid liberated in response to carbamoylcholine was measured by gas chromatography-mass spectrometry, and the time course of stimulated arachidonate accumulation paralleled that of inositol phosphate accumulation and amylase release. These observations suggest that in exocrine pancreas, endogenous arachidonic acid serves as a negative feedback regulator of phosphoinositide turnover.

Animals↗
PubMed1987

Mitogen-stimulated release of inositol phosphates in human fibroblasts.

Mitogenic stimulation of quiescent human fibroblasts (HSWP) with a growth factor mixture (consisting of epidermal growth factor (EGF), insulin, bradykinin, and vasopressin) rapidly induces an increase in Na influx via a Ca-mediated activation of an amiloride-sensitive Na/H exchanger. Inositol phosphates (specifically inositol-1',4',5'-phosphate) have been implicated in mediating the mobilization of intracellular Ca stores in other cell types and we have now completed a detailed analysis of the mitogen-induced release of inositol phosphates in HSWP cells. Stimulation of inositol trisphosphate release is rapid (within 5 s) and reaches a maximum level (416-485% basal) within 10-15 s after the addition of growth factor mixture. Inositol bisphosphate and inositol monophosphate reach maximum levels by 30 s (1257% basal) and 60 s (291% basal), respectively. Levels of all three compounds then decay toward basal levels but remain elevated (150-350% of basal levels) after 10 min of incubation with mitogens. The effects of different combinations of these growth factors and of the bee venom peptide, melittin, have also been determined. We have also found that 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate, which prevents the mitogen-induced rise in intracellular calcium activity and activation of Na influx, does not alter the mitogen-stimulated accumulation of inositol trisphosphate. In addition, the calcium ionophore A23187, which increases cytosolic Ca activity and induces a Na influx, does not stimulate the release of inositol trisphosphate. Assays performed in the presence of lithium, which inhibits inositol phosphate monophosphatase, promotes the prolonged and enhanced accumulation of inositol monophosphate. Treatment with the phospholipase inhibitor mepacrine or pretreatment with dexamethasone reduces the amount of inositol phosphates released upon mitogenic stimulation. Hence mitogenic stimulation of HSWP cells leads to the rapid stimulation of inositol phosphate release via a calcium-independent mechanism and suggests inositol trisphosphate as a candidate to mediate the release of intracellular calcium stores which is involved in the processes responsible for the activation of the Na/H exchanger.

Bradykinin↗
PubMed1986

Non-competitive inhibition of myo-inositol transport in cultured bovine retinal capillary pericytes by glucose and reversal by Sorbinil.

myo-Inositol transport by retinal capillary pericytes in culture was characterized. The major myo-inositol transport process was sodium-dependent, ouabain-sensitive, and saturable at 40 mM, indicating a carrier-mediated process. The sodium ion concentration required to produce one-half the maximal rate of myo-inositol uptake ([Na+]0.5) did not show dependence on the external myo-inositol concentration (22.3 mM sodium for 0.005 mM myo-inositol; 18.2 mM sodium for 0.05 mM myo-inositol). myo-Inositol transport was an energy-dependent, active process functioning against a myo-inositol concentration gradient. The kinetics of the sodium-dependent system fitted a 'velocity type' co-transport model where binding of sodium ion to the carrier increased the velocity (Vmax 28 to 313 pmol myo-inositol/micrograms DNA per 20 min when [Na+] varied from 9 to 150 mM) but not the affinity for myo-inositol (Km 0.92 to 0.83 mM when [Na+] varied from 9 to 150 mM). Metabolizable hexoses (D-glucose or D-galactose; greater than 5 mM) inhibited myo-inositol uptake. Dixon-plot analysis indicated that the inhibition was non-competitive with a Ki of 22.7 mM for D-glucose and 72.6 mM for D-galactose. The inhibition was significantly reversed by Sorbinil (0.1 mM), an aldose reductase inhibitor. In contrast, high concentrations of non-metabolizable hexoses (L-glucose, 3-O-methyl-D-glucose), or partially metabolizable 2-deoxy-D-glucose, did not significantly inhibit myo-inositol uptake. The inhibitory effect of D-glucose or D-galactose on myo-inositol transport appeared to be related to glucose or galactose metabolism via the polyol pathway.

3-O-Methylglucose↗
PubMed2002

Myo-inositol-1-phosphate (MIP) synthase: a possible new target for antibipolar drugs.

Inositol metabolism is well characterized in yeast at a molecular level, and yeast is the only eukaryote in which genetic, molecular and functional genomic approaches to identify lithium. valproate and inositol targets may be combined readily. It has been shown that lithium inhibits yeast inositol monophosphatase (encoded by INM1 and INM2), and both valproate and lithium reduce intracellular inositol. Unlike lithium, valproate causes a decrease in intracellular inositol-1-phosphate as well. suggesting that myo-inositol-1-P (MIP) synthase is a site of valproate action in the yeast PI cycle. MIP synthase is the rate-limiting step in inositol biosynthesis and is highly regulated in response to inositol. Yeast genes that are affected by both lithium and valproate in the phosphoinositide pathways (INO1 increased over 10-fold, INO2 increased twofold and INM1 decreased about twofold) have been identified. It has also been reported previously that both lithium and inositol mildly up-regulate IMPA1 (encoding mammalian inositol monophosphatase) expression in human cells. These findings indicate that IMPA is regulated only mildly by lithium, and therefore may not be the major target in the inositol pathway. Given the substantial evidence for the role of inositol in the mechanism of action of lithium and valproate. the opposing and mild effects of lithium on the genes encoding inositol monophosphatase in yeast and human cells, but the powerful effect of lithium and valproate on INO1 in yeast, it is hypothesized that human hIANO1 is a factor in the psychopharmacology of mood stabilizers.

Animals↗
PubMed1988

Epidermal-growth-factor-induced formation of inositol phosphates in human A431 cells. Differences from the effect of bradykinin.

In human A431 epidermoid carcinoma cells, epidermal growth factor (EGF) rapidly stimulates the breakdown of inositol phospholipids and raises cytoplasmic free [Ca2+]. In this paper, we investigate the action of EGF on inositol phosphate metabolism, and we compare it with the previously described effects of bradykinin on the same cell system [Tilly, van Paridon, Verlaan, Wirtz, de Laat & Moolenaar (1987) Biochem. J. 244, 129-135]. In cells prelabelled with [3H]inositol, EGF slowly but persistently (for at least 30 min) stimulates the formation of [3H]inositol phosphates, whereas bradykinin causes an immediate but transient release of inositol phosphates, which lasts for only a few minutes. The EGF effect is additive to bradykinin stimulation and does not require extracellular Ca2+. In contrast, inositol phosphate formation induced by Ca2+-ionophore A23187 has an absolute requirement for external Ca2+. Treatment of the cells with 12-O-tetradecanoylphorbol 13-acetate completely abolishes the response to EGF and to sub-optimal doses of bradykinin, suggesting a negative-feedback function of protein kinase C. Pretreatment of the cells with pertussis toxin has no effect on inositol phosphate formation induced by either EGF or bradykinin. Unlike bradykinin, EGF stimulates very little accumulation of inositol 1,4,5-trisphosphate, with only a small and rather variable release of Ca2+ from intracellular stores. EGF rapidly but transiently increases inositol 1,3,4-trisphosphate and 1,3,4,5-tetrakisphosphate, but the effects are much smaller than those of bradykinin. In addition, EGF increases both inositol mono- and bis-phosphate. At 10 min after EGF addition, inositol monophosphate, unlike the other inositol phosphates, is still increasing. It is concluded that the EGF-dependent pattern of stimulation is different from that observed in bradykinin-stimulated A431 cells, suggesting that there are separate mechanisms of inositol-lipid hydrolysis involved.

Bradykinin↗
PubMed1992

Inositol supplementation in premature infants with respiratory distress syndrome.

BACKGROUND: Inositol influences cellular function and organ maturation. Feeding premature infants inositol-rich breast milk increases their serum inositol concentrations. Whether inositol supplementation benefits infants receiving fluids for parenteral nutrition, which are inositol-free, is not known. METHODS: We carried out a placebo-controlled, randomized, double-blind trial to determine the effects of administering inositol (80 mg per kilogram of body weight per day) during the first five days of life to 221 infants with respiratory distress syndrome who were receiving parenteral nutrition (gestational age, 24 to 32 weeks; birth weight, less than 2000 g). All the infants were treated with mechanical ventilation and some with surfactant as well. The primary end point was survival at 28 days without bronchopulmonary dysplasia. RESULTS: The 114 patients given inositol had significantly lower mean requirements for inspiratory oxygen (P less than 0.01) and mean airway pressure (P less than 0.05) from the 12th through the 144th hour of life than did the 107 infants given placebo. Eighty-one infants given inositol and 51 given placebo survived without bronchopulmonary dysplasia (71 vs. 55 percent; P = 0.005). In the 65 infants given surfactant, however, inositol had no effect on the degree of respiratory failure. Thirteen infants given inositol and 21 given placebo had retinopathy of prematurity (13 vs. 26 percent; P = 0.022); none of the infants given inositol had stage 4 disease, whereas 7 of those given placebo did (0 vs. 9 percent; P = 0.012). Among the infants given placebo, those who had poor outcomes (death, bronchopulmonary dysplasia, or stage 4 retinopathy of prematurity) had lower serum inositol concentrations during days 2 through 7 than those who had good outcomes (P less than 0.01). CONCLUSIONS: The administration of inositol to premature infants with respiratory distress syndrome who are receiving parenteral nutrition during the first week of life is associated with increased survival without bronchopulmonary dysplasia and with a decreased incidence of retinopathy of prematurity.

Bronchopulmonary Dysplasia↗
PubMed2000

Inositol stereoisomers stabilize an oligomeric aggregate of Alzheimer amyloid beta peptide and inhibit abeta -induced toxicity.

Inositol has 8 stereoisomers, four of which are physiologically active. myo-Inositol is the most abundant isomer in the brain and more recently shown that epi- and scyllo-inositol are also present. myo-Inositol complexes with Abeta42 in vitro to form a small stable micelle. The ability of inositol stereoisomers to interact with and stabilize small Abeta complexes was addressed. Circular dichroism spectroscopy demonstrated that epi- and scyllo- but not chiro-inositol were able to induce a structural transition from random to beta-structure in Abeta42. Alternatively, none of the stereoisomers were able to induce a structural transition in Abeta40. Electron microscopy demonstrated that inositol stabilizes small aggregates of Abeta42. We demonstrate that inositol-Abeta interactions result in a complex that is non-toxic to nerve growth factor-differentiated PC-12 cells and primary human neuronal cultures. The attenuation of toxicity is the result of Abeta-inositol interaction, as inositol uptake inhibitors had no effect on neuronal survival. The use of inositol stereoisomers allowed us to elucidate an important structure-activity relationship between Abeta and inositol. Inositol stereoisomers are naturally occurring molecules that readily cross the blood-brain barrier and may represent a viable treatment for AD through the complexation of Abeta and attenuation of Abeta neurotoxic effects.

Alzheimer Disease↗
PubMed1983

Tissue content and metabolism of myo-inositol in normal and lipodystrophic gerbils.

Experiments were conducted to evaluate the effect of diet and sex difference on the development of an intestinal lipodystrophy due to myo-inositol deficiency. Tissue contents of free and lipid-bound myo-inositol as well as the activities of L-myo-inositol-l-phosphate synthase (EC 5.5.1.4) and phosphatase (EC 3.1.3.25), and myo-inositol oxygenase (EC 1.13.99.1) were determined in male and female gerbils under various conditions. The enzyme study proved that the essentiality of dietary myo-inositol for this species was not due to the lack of such enzyme activity. The lower susceptibility of male gerbils to myo-inositol deficiency could be explained by the contribution of the biosynthesis of myo-inositol in the testis, as shown by a difference between intact and castrated animals. Although feeding coconut oil to the myo-inositol-deficient female gerbils produced greater myo-inositol depletion as well as more severe intestinal lesion than the feeding of safflower oil, the difference in myo-inositol status could be only in part responsible for different degrees of lipodystrophy. Additionally, neither dietary type of fat nor exogenous myo-inositol altered the activities of either hepatic or intestinal synthase and phosphatase, or kidney oxygenase. Thus, this study indicates that both sex and dietary factors might influence myo-inositol status to varying extents, but the diet-induced change in tissue myo-inositol was not reflected by the enzyme activity as measured in vitro.

Animals↗
PubMed1996

Inhibition by cyclic AMP of basal and induced inositol phosphate production in cultured aortic smooth muscle cells from Wistar-Kyoto and spontaneously hypertensive rats.

OBJECTIVE: To investigate inositol phosphate formation and its modulation by the cyclic AMP (cAMP) pathway in cultured aortic smooth muscle cells from spontaneously hypertensive rats (SHR). METHODS: Phenylephrine was used to stimulate inositol phosphate formation in cultured aortic smooth muscle cells from SHR and Wistar-Kyoto (WKY) rats. The smooth muscle cells from passages 6-14 were prelabelled with myo-[2-3H]-inositol (1.9 x 10(5) Bq/ml for 24 h) and inositol phosphate formation was measured after exposure to agonist for 45 min. (-)isoproterenol or forskolin-induced cAMP formation was also evaluated using a radioimmunoassay method. RESULTS: The basal level of inositol phosphate formation in smooth muscle cells from SHR was higher than that observed in smooth muscle cells from WKY rats. Phenylephrine increased the formation of inositol phosphates in a concentration-dependent manner (0.1-100 mumol/l). In the presence of 100 mumol/l phenylephrine, the increase in inositol phosphate formation was significantly greater in smooth muscle cells from SHR (214 +/- 6%) than that observed in smooth muscle cells from WKY rats (156 +/- 8%). When the cells were pretreated with 1 mmol/l 8-bromoadenosine 3':5'-cyclic monophosphate or with 10 mumol/l forskolin for 45 min, the basal production of inositol phosphates in smooth muscle cells both from SHR and from WKY rats was significantly and similarly decreased by about 20%. In the presence of 1 mmol/l 8-bromoadenosine 3':5'-cyclic monophosphate, 100 mumol/l phenylephrine-induced inositol phosphate formation was similarly decreased by 33 +/- 4 and 30 +/- 3% in smooth muscle cells from SHR and from WKY rats, respectively, whereas, in the presence of 10 mumol/l forskolin, inositol phosphate formation was reduced by 25 +/- 3 and 27 +/- 5%, respectively, in those cells. In contrast, isoproterenol induced less inhibition of phenylephrine-induced inositol phosphate formation in smooth muscle cells from SHR (14 +/- 2%) than it did in those from WKY rats (25 +/- 4.5%). Although there was no significant difference in basal or forskolin-induced cAMP accumulation between smooth muscle cells from SHR and those from WKY rats. (-)isoproterenol-induced cAMP accumulation was significantly lower in smooth muscle cells from SHR. CONCLUSION: A marked inhibitory effect of cAMP on the alpha 1-adrenoceptor-mediated inositol phosphate signal transduction pathway was demonstrated in smooth muscle cells of SHR and of WKY rats. Decreased cAMP formation with beta-adrenergic stimulation and increased inositol phosphate formation with alpha-adrenergic stimulation in SHR smooth muscle cells may both contribute to the dominant alpha 1-adrenergic activity observed in SHR.

Animals↗