Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “INOSITOL”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 343 records · Page 19Linked to original sources
PubMed1997

Binding and activity of the nine possible regioisomers of myo-inositol tetrakisphosphate at the inositol 1,4,5-trisphosphate receptor.

All 9 racemic regioisomers (15 enantiomerically) of myo-inositol tetrakisphosphates (IP4s): DL-Ins(1,2,4,5)P4 [A], DL-Ins(1,2,4,6)P4 [B], Ins(1,2,3,5)P4 [C], Ins(1,3,4,6)P4 [D], Ins(2,4,5,6)P4 [E], DL-Ins(1,3,4,5)P4 [F], DL-Ins(1,2,5,6)P4 [G], DL-Ins(1,2,3,4)P4 [H] and DL-Ins(1,4,5,6)P4 [I] [Chung S-K., Chang Y-T. Synthesis of all possible regioisomers of myo-inositol tetrakisphosphate. J Chem Soc Chem Commun 1995; 11-13] were investigated for their ability to bind to the D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] receptor in bovine adrenal cortical membranes, and for their ability to mobilize 45Ca2+ from Ins(1,4,5)P3-sensitive Ca2+ stores in permeabilized Chinese hamster ovary (CHO) cells. DL-Ins(1,2,4,5)P4 (Ki = 11 nM) bound to Ins(1,4,5)P3 receptors with an affinity only 2-fold lower than Ins(1,4,5)P3 (Ki = 6 nM). Ins(1,2,3,5)P4, Ins(1,3,4,6)P4, Ins(2,4,5,6)P4, DL-Ins(1,3,4,5)P4, DL-Ins(1,2,3,4)P4 and DL-Ins(1,4,5,6)P4 bound with affinities of between 0.4-0.7 microM. DL-Ins(1,2,4,6)P4 and DL-Ins(1,2,5,6)P4 bound to the Ins(1,4,5)P3 receptor with low affinity (approximately 2-3 microM). All but one of the IP4s mediated release of 45Ca2+ from stores of permeabilized CHO cells with a similar rank order of potency as that for Ins(1,4,5)P3 receptor binding, being between 16-fold and 50-fold less potent at releasing 45Ca2+ compared with their apparent binding affinities to the Ins(1,4,5)P3 receptor. The notable exception was Ins(1,2,3,5)P4, which showed an approximately 200-fold lower potency compared with its affinity for the Ins(1,4,5)P3 receptor. Ins(1,2,3,5)P4 may be a useful lead compound for the rational design of novel synthetic Ins(1,4,5)P3 analogues possessing structure-activity profiles with relatively high binding affinity, but low intrinsic efficacy, and hence partial agonists and antagonists at the Ins(1,4,5)P3 receptor.

Animals↗
PubMed1988

Detection of inositol 1,4,5-trisphosphate kinase in retina. A direct demonstration of phosphorylation of inositol 1,4,5-trisphosphate by ATP.

The metabolism of myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] consists of two pathways: dephosphorylation by 5-phosphomonoesterase(s) produces inositol 1,4-bisphosphate, and phosphorylation by Ins(1,4,5)P3 3-kinase yields inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4]. The requirements for Ins(1,4,5)P3 kinase activity in retina were characterized. Apparent Km values for ATP and Ins(1,4,5)P3 are 1.4 mM and 1.3 microM respectively. A direct demonstration of phosphorylation of Ins(1,4,5)P3 by [gamma-32P]ATP was achieved. Characterization of the 32P-labelled product revealed that it had the expected chromatographic and electrophoretic properties of Ins(1,3,4,5)P4.

Adenosine Triphosphate↗
PubMed1991

Relationship between the calcium-mobilizing action of inositol 1,4,5-trisphosphate in permeable AR4-2J cells and the estimated levels of inositol 1,4,5-trisphosphate in intact AR4-2J cells.

Various experimental strategies were employed in an effort to explain the previously reported [Horstman, Takemura & Putney (1988) J. Biol. Chem. 263, 15297-15303] paradoxically high levels of inositol 1,4,5-trisphosphate [(1,4,5)IP3] in resting and substance-P-stimulated AR4-2J cells. The concentration-effect curves for substance-P-induced [3H](1,4,5)IP3 formation in [3H]inositol-labelled cells and substance-P-induced increase in intracellular [Ca2+] were essentially superimposable, suggesting that formation of (1,4,5)IP3 is limiting for cellular Ca2+ mobilization. In electrically permeabilized AR4-2J cells, (1,4,5)IP3 and other inositol polyphosphates stimulated Ca2+ release with potencies similar to those reported for other cell types, including the parent pancreatic acinar cell. Compartmentalization of basal (1,4,5)IP3 was suggested by the fact that this material was stable in the presence of antimycin A, although this toxin completely blocked agonist stimulation of phospholipase C. However, subcellular fractionation as well as permeabilization of the cells with Staphylococcus aureus alpha-toxin failed to provide evidence for binding or sequestration of [3H](1,4,5)IP3 in AR4-2J cells. The density of (1,4,5)IP3 receptors in AR4-2J cells was not sufficiently large to impose non-linearity in the relationship between (1,4,5)IP3 concentration and (1,4,5)IP3-induced Ca2+ release. Thus the apparent high concentrations of (1,4,5)IP3 in resting and stimulated AR4-2J cells are not indicative of atypically low sensitivity or high concentration of (1,4,5)IP3 receptors, nor is there evidence for compartmentalization of (1,4,5)IP3 outside of the cytoplasm in these cells. It is possible that soluble factors in the cytoplasm of AR4-2J cells regulate the free concentration of (1,4,5)IP3 or the sensitivity of receptors to (1,4,5)IP3.

Animals↗
PubMed1993

Ambient glucose and aldose reductase-induced myo-inositol depletion modulate basal and carbachol-stimulated inositol phospholipid metabolism and diacylglycerol accumulation in human retinal pigment epithelial cells in culture.

Physiological hyperglycemia has been speculated to alter phosphoinositide (PPI; inositol phospholipid) signal transduction in cells prone to diabetic complications by two separate mass-action mechanisms with antiparallel putative effects on diacylglycerol (DAG): (i) sorbitol-induced depletion of myo-inositol leads to diminished PPI synthesis and turnover and DAG release, and (ii) elevated glucose-derived DAG precursors enhance de novo DAG synthesis. Because the first mechanism is mediated by aldose reductase (AR2), which converts glucose to sorbitol, the effects of glucose on basal and stimulated PPI signaling were explored in lines of cultured human retinal pigment epithelial cells differing widely in their basal AR2 gene expression and enzymatic activity. The results suggest that the effects of glucose on PPI signaling vary inversely with the level of AR2 activity and parallel the extent of AR2-induced myo-inositol depletion.

Aldehyde Reductase↗
PubMed2000

Ca(2+)-activated but not G protein-mediated inositol phosphate responses in rat neonatal cardiomyocytes involve inositol 1,4, 5-trisphosphate generation.

Inositol phosphate (InsP) responses to receptor activation are assumed to involve phospholipase C cleavage of phosphatidylinositol 4,5-bisphosphate to generate Ins(1,4,5)P(3). However, in [(3)H]inositol-labeled rat neonatal cardiomyocytes (NCM) both initial and sustained [(3)H]InsP responses to alpha(1)-adrenergic receptor stimulation with norepinephrine (100 microM) were insensitive to the phosphatidylinositol 4,5-bisphosphate-binding agent neomycin (5 mM). Introduction of 300 microM unlabeled Ins(1,4, 5)P(3) into guanosine 5'-3-O-(thio)triphosphate (GTPgammaS)-stimulated, permeabilized [(3)H]inositol-labeled NCM increased [(3)H]Ins(1,4,5)P(3) slightly but did not significantly reduce levels of its metabolites [(3)H]Ins(1,4)P(2) and [(3)H]Ins(4)P, suggesting that these [(3)H]InsPs are not formed principally from [(3)H]Ins(1,4,5)P(3). In contrast, the calcium ionophore A23187 (10 microM) provoked [(3)H]InsP responses in intact NCM which were sensitive to neomycin, and elevation of free calcium in permeabilized NCM led to [(3)H]InsP responses characterized by marked increases in [(3)H]Ins(1,4,5)P(3) (2.9 +/- 0.2% of total [(3)H]InsPs after 20 min of high Ca(2+) treatment in comparison to 0. 21 +/- 0.05% of total [(3)H]InsPs accumulated after 20 min of GTPgammaS stimulation). These data provide evidence that Ins(1,4, 5)P(3) generation is not a major contributor to G protein-coupled InsP responses in NCM, but that substantial Ins(1,4,5)P(3) generation occurs under conditions of Ca(2+) overload. Thus in NCM, Ca(2+)-induced Ins(1,4,5)P(3) generation has the potential to worsen Ca(2+) overload and thereby aggravate Ca(2+)-induced electrophysiological perturbations.

Animals↗
PubMed1989

Regulatory role of retinoic acid on cultured mouse keratinocyte inositol phospholipid metabolism: dose-dependent release of inositol triphosphate.

The incorporation of precursor 14C-myoinositol into the three cellular inositol phospholipids (PtdIns, PtdInsP, and PtdInsP2) of cultured, rapidly proliferating keratinocytes is significantly enhanced by the exogenous addition of a high concentration (1 X 10(-7) M) of all-trans retinoic acid or its analog 13-Cis analog, whereas a similar incubation with a low concentration (1 X 10(-10) M) of the same retinoid resulted in an insignificant incorporation of the radio-precursor into the three inositol phospholipids. Incorporation was most marked into the more phosphorylated PtdIns4P and PtdIns4,5P2. These results indicate that retinoic acid affects the biosynthesis of the inositol phospholipids at high concentrations. In contrast, the hydrolysis of 14C-PtdIns4,5P2 and release of 14C-InsP3 from the prelabeled keratinocytes is markedly enhanced by a low physiologic concentration (1 X 10(-10) M) of retinoic acid or its 13-Cis analog. The hydrolysis is rapid, with an accompanying elevated transient release of 14C-InsP3. High concentration (1 X 10(-5) M), on the other hand, supresses 14C-InsP3 release. These results taken together underscore a bifunctional, dose-dependent effect of both the all-trans-RA and its 13-Cis analog on the synthesis and hydrolysis of keratinocyte PtdIns4,5P2. Furthermore, the results suggest that at low physiologic concentrations, these retinoids may function as agonists to perturb the membrane resulting in induced rapid hydrolysis of cellular PtdIns4,5P2, which is coupled to a "transient" generation of InsP3 (an intracellular second messenger). The rapid formation of this putative "second messenger" may in turn play a role in the cellular proliferative or differentiating biochemical events in the murine keratinocytes.

Animals↗
PubMed1989

Intracellular localization of inositol-phospholipid-metabolizing enzymes in rabbit fast-twitch skeletal muscle. Can D-myo-inositol 1,4,5-trisphosphate play a role in excitation-contraction coupling?

Rabbit fast-twitch skeletal muscle microsomes have been separated by isopycnic centrifugation on a linear sucrose gradient into triads and light sarcoplasmic reticulum. In both fractions phosphatidylinositol-kinase activity is found [Varsányi et al. (1986) Biochem. Biophys. Res. Commun. 138, 1395]. In contrast, phosphatidylinositol-4-phosphate kinase is nearly exclusively associated with triads. The phosphatidylinositol-4,5-bisphosphate-phosphodiesterase activity shows a biphasic distribution: approximately 50% of the activity is associated with triads and 50% appears in the overlay. Triads have been broken mechanically into transverse tubules and terminal cisternae, then separated by isopycnic sucrose-gradient centrifugation. Both fractions exhibit phosphatidylinositol-kinase activity; the activities of phosphatidylinositol-4-phosphate kinase and phosphatidylinositol-4,5-bisphosphate phosphodiesterase are associated mainly with the transverse tubules. Consequently, in rabbit fast-twitch skeletal muscle all necessary enzymes for production of D-myo-inositol 1,4,5-trisphosphate are associated with transverse tubules. Phosphatidylinositol-4,5-bisphosphate phosphodiesterase associated with triads shows a pH optimum at 6.8. The enzyme is maximally active between pCa 5 and pCa 4. Mg2+ inhibits the enzyme activity half-maximally at about 1 mM. Guanine-nucleotide-binding proteins seem not to be involved in the regulation of enzyme activity; guanosine 5'-[gamma-thio]triphosphate does not influence phosphatidylinositol-4,5-bisphosphate phosphodiesterase activity. It correlates well with the observation that neither alpha 1-adrenergic nor muscarinic receptors have been found in fast-twitch rabbit skeletal muscle. On basis of the respective enzyme activities estimations on maximal phosphatidylinositol turnover were made and a possible involvement of this signal pathway in excitation-contraction coupling has been discussed. Furthermore, calculations show that during a single twitch D-myo-inositol 1,4,5-trisphosphate concentration does not reach more than 2 nM. However, during a 4-s tetanus D-myo-inositol 1,4,5-trisphosphate can accumulate to a level which could effect force generation [Thieleczek and Heilmeyer (1986) Biochem. Biophys. Res. Commun. 135, 662] and aldolase distribution (Thieleczek et al., unpublished results).

Animals↗
PubMed1993

Inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate binding sites in smooth muscle.

1. We have previously demonstrated that activation of M3 muscarinic receptors increases inositol 1,4,5-trisphosphate (InsP3) and inositol 1,3,4,5-tetrakisphosphate (InsP4) accumulation in colonic smooth muscle. 2. In the present study, we demonstrate the existence of InsP3 and InsP4 binding sites in colonic circular smooth muscle by use of radioligand binding methods. Both [3H]-InsP3 and [3H]-InsP4 bound rapidly and reversibly to a single class of saturable sites in detergent-solubilized colonic membranes with affinities of 5.04 +/- 1.03 nM and 3.41 +/- 0.78 nM, respectively. The density of [3H]-InsP3 binding sites was 335.3 +/- 19.3 fmol mg-1 protein which was approximately 2.5 fold greater than that of [3H]-InsP4 sites (127.3 +/- 9.1 fmol mg-1 protein). 3. The two high affinity inositol phosphate binding sites exhibited markedly different pH optima for binding of each radioligand. At pH 9.0, specific [3H]-InsP3 binding was maximal, whereas [3H]-InsP4 binding was only 10% that of [3H]-InsP3. Conversely, at pH 5.0, [3H]-InsP4 binding was maximal, while [3H]-InsP3 binding was reduced to 15% of its binding at pH 9.0. 4. InsP3 was about 20 fold less potent (KI = 50.7 +/- 8.3 nM) than InsP4 in competing for [3H]-InsP4 binding sites and could compete for only 60% of [3H]-InsP4 specific binding. InsP4 was also capable of high affinity competition with [3H]-InsP3 binding (KI = 103.5 +/- 1.5 nM), and could compete for 100% of [3H]-InsP3 specific binding. 5. [3H]-InsP3 binding in subcellular fractions separated by discontinuous sucrose density gradients followed NADPH-cytochrome c reductase activity, suggesting an intracellular localization for the majority of InsP3 receptors in this tissue, whereas [3H]-InsP4 binding appeared to be equally distributed between plasma membrane and intracellular membrane populations.6. These results suggest the existence of distinct and specific InsP3 and InsP4 binding sites which may represent the physiological receptors for these second messengers; differences in the subcellular distribution of these receptors may contribute to differences in their putative physiological roles.

Adenosine Triphosphate↗
PubMed1994

Second messenger specificity of the inositol trisphosphate receptor: reappraisal based on novel inositol phosphates.

To further understand how the second messenger D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] interacts with its intracellular receptor, we injected 47 highly purified inositol phosphate (InsP) positional isomers in Xenopus oocytes and compared their potency in releasing intracellular Ca2+. The potency of the Ca(2+)-releasing InsPs spanned four orders of magnitude. Seven compounds, including the novel inositol 1,2,4,5-tetrakisphosphate [D/L-Ins (1,2,4,5)P4] and D/L-Ins(1,4,6)P3, had a very high potency. All of these highly active InsPs shared the following structure: two D-trans-equatorial phosphates (eq-P) and one equatorial hydroxyl (eq-OH) attached to ring carbons D-4, D-5, and D-6 (or to the structurally equivalent D-1, D-6, and D-5 carbons). This permissive structure was not sufficient for Ca2+ release, because it was also found in two inactive compounds, Ins(1,6)P2 and Ins(1,3,6)P3. To be active, InsPs also required the structural equivalent of a D-3 eq-OH and/or a D-1 eq-P. Together, our data reveal how the structure of the InsP molecule affects its ability to release Ca2+.

Animals↗
PubMed1988

Studies of the Ca2+ requirements for glucose- and carbachol-induced augmentation of inositol trisphosphate and inositol tetrakisphosphate accumulation in digitonin-permeabilized islets. Evidence for a glucose recognition site in insulin secretion.

The metabolism of D-glucose is believed to initiate and regulate insulin secretion by islet beta-cells, although the identity of the metabolite which couples glucose metabolism to the cellular events involved in insulin secretion is unknown. An alternative hypothesis involves the presence of a glucoreceptor for which there has been no biochemical evidence. We have investigated whether glucose recognition by the beta-cell is coupled to phospholipase C. We have used digitonin-permeabilized, [3H]inositol-prelabeled islets to study glucose and carbachol activation of phospholipase C. In this model, carbachol recognition by its muscarinic receptor was coupled to phospholipase C activation. D-Glucose (but not L-glucose) also stimulated phospholipase C activity in these permeabilized islets. This effect was not due to glucose metabolism since glucose 6-phosphate did not affect phospholipase C activity and since phosphorylation of [3H]glucose was not detectable in digitonin-permeabilized islets. Glucose had no effect on the myo-inositol-1,4,5-trisphosphate-5-phosphatase or 3-kinase activities. In the absence of agonist, free Ca2+ concentrations between 0.1 and 1 microM (as determined with a Ca2+-specific electrode) did not influence phospholipase C activity. Stimulation of phospholipase C activity by either carbachol or glucose required Ca2+ in the submicromolar range and was optimal at 0.5 microM free Ca2+.myo-Inositol-1,3,4,5-tetrakisphosphate production from permeabilized islets was synergistically augmented by Ca2+ (0.5-10 microM) and glucose. Phospholipase C activity in islets is therefore not directly activated by free Ca2+ concentrations in the submicromolar range. Furthermore, glucose per se activates phospholipase C activity independently of glucose metabolism. A working hypothesis based on these findings is that glucose is recognized by a site which is coupled to phospholipase C in islets.

Animals↗
PubMed1993

Stimulation of nuclear protein kinase C leads to phosphorylation of nuclear inositol 1,4,5-trisphosphate receptor and accelerated calcium release by inositol 1,4,5-trisphosphate from isolated rat liver nuclei.

Rat liver nuclei inositol 1,4,5-trisphosphate receptor (Malviya, A.N., Rogue, P., and Vincendon, G. (1990) Proc. Natl. Acad. Sci U.S.A. 87, 9270-9274) is identified as a 220-kDa protein on Western blotting employing two types of antibodies (anti-goat and anti-rabbit) raised against purified rat brain inositol 1,4,5-trisphosphate receptor (IP3R). Nuclear IP3R does not seem identical with microsomal IP3R in rat liver. Treatment of isolated rat liver nuclei with 12-O-tetradecanoylphorbol-13-acetate stimulates native protein kinase C activity severalfold. Nuclear IP3R is phosphorylated by stimulated protein kinase C, with accelerated as well as enhanced maximum 45Ca2+ release by inositol 1,4,5-trisphosphate from isolated nuclei, without altering 1,4,5-trisphosphate binding characteristics (KD and Bmax). Stimulation of nuclear protein kinase C is found physiologically relevant since lamin B2, a nuclear protein, is concomitantly phosphorylated. These data deal with functional consequences of nuclear IP3R phosphorylation by native protein kinase C in isolated rat liver nuclei. It is postulated that phosphorylation of nuclear IP3R, probably dephosphorylation also, subserves a key mechanism in nuclear calcium homeostasis.

Animals↗
PubMed2005

Interaction of the catalytic domain of inositol 1,4,5-trisphosphate 3-kinase A with inositol phosphate analogues.

The levels of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] in the cytoplasm are tightly regulated by two enzymes, Ins(1,4,5)P3 3-kinase and type I Ins(1,4,5)P3 5-phosphatase. The catalytic domain of Ins(1,4,5)P3 3-kinase (isoenzymes A, B and C) is restricted to approximately 275 amino acids at the C-terminal end. We were interested in understanding the catalytic mechanism of this key family of enzymes in order to exploit this in inhibitor design. We expressed the catalytic domain of rat Ins(1,4,5)P3 3-kinase A in Escherichia coli as a His- and S-tagged fusion protein. The purified enzyme was used in an Ins(1,4,5)P3 kinase assay to phosphorylate a series of inositol phosphate analogues with three or four phosphate groups. A synthetic route to D-2-deoxy-Ins(1,4,5)P3 was devised. D-2-Deoxy-Ins(1,4,5)P3 and D-3-deoxy-Ins(1,4,6)P3 were potent inhibitors of the enzyme, with IC50 values in the micromolar range. Amongst all analogues tested, only D-2-deoxy-Ins(1,4,5)P3 appears to be a good substrate of the Ins(1,4,5)P3 3-kinase. Therefore, the axial 2-hydroxy group of Ins(1,4,5)P3 is not involved in recognition of the substrate nor does it participate in the phosphorylation mechanism of Ins(1,4,5)P3. In contrast, the equatorial 3-hydroxy function must be present in that configuration for phosphorylation to occur. Our data indicate the importance of the 3-hydroxy function in the mechanism of inositol trisphosphate phosphorylation rather than in substrate binding.

Animals↗
PubMed1994

Effect of insulin on the incorporation of 3H-inositol into the inositol phospholipids (PI, PIP, PIP2) and glycosyl-phosphatidylinositols (GPIs) of tetrahymena pyriformis.

The unicellular tetrahymena contains inositol phospholipids (PI, PIP, PIP2) and GPIs. Treatment with 10(-5) M insulin decreases the total 3H-inositol incorporation and incorporation into PI. 24 h after 10(-6) M insulin treatment there is an elevation of these parameters. Second treatment with 10(-6) M insulin doubles and 10(-5) M decreases these levels. This means that the effect on phosphoinositide turnover by insulin in Tetrahymena is rather concentration dependent. Inositol incorporation into GPIs is also influenced by insulin.

Animals↗
PubMed1986

Effect of hyperglycemia on sorbitol and myo-inositol content of cultured rat conceptus: failure of aldose reductase inhibitors to modify myo-inositol depletion and dysmorphogenesis.

Growth retardation and dysmorphogenesis were seen in the rat conceptus following culture from day 9.5 to 11.5 of development in the presence of increased amounts of glucose. Sorbitol accumulated in the conceptus during the hyperglycemia whereas total protein, DNA, and free myo-inositol decreased. Similar glucose-related compositional changes were present in separated embryos and extra-embryonic membranes suggesting that all portions of the conceptus participate in the alterations. The aldose reductase inhibitors Sorbinil and Statil obtunded the rises in sorbitol but did not modify the increased incidence of malformations and the fall in DNA, protein and myo-inositol. Thus, the aldose reductase pathway may function in the early post-implantation rat conceptus but the resultant accumulation of sorbitol does not appear to contribute to the growth-retarding, dysmorphogenic, and myo-inositol-depleting effects of hyperglycemia.

Aldehyde Reductase↗
PubMed1993

Inositol treatment raises CSF inositol levels.

Inositol is a key precursor for synthesis of phosphatidylinositol in a major second messenger signalling system. It is biologically active in syndromes such as respiratory distress syndrome but has been thought to be excluded from CNS by the blood-brain barrier. Oral inositol treatment of 8 patients is shown to significantly increase CSF inositol by almost 70%, suggesting possible CNS therapeutic applications of this compound and possible CNS side-effects of systemic therapy.

Adult↗
PubMed1986

Membrane current responses to intracellular injections of inositol 1,3,4,5-tetrakisphosphate and inositol 1,3,4-trisphosphate in NG108-15 hybrid cells.

Iontophoretic injections of inositol 1,4,5-trisphosphate inside neuroblastoma X glioma NG108-15 hybrid cells evoked an outward K+ current across the outer cell membrane, probably activated by the release of intracellular Ca2+. No such current was produced by equivalent intracellular injections of inositol 1,3,4-trisphosphate or inositol 1,3,4,5-tetrakisphosphate. Instead, these compounds evoked an inward current with a reversal potential of about -20 mV, and which may therefore be due to a non-specific cation conductance. This suggests that these derivatives are unable to release sufficient Ca2+ to activate the Ca2+-dependent K+ current in these cells.

Animals↗
PubMed2005

Solid and solution state conformations of (+/-)-3-O-acetyl-1,2:4,5-di-O-isopropylidene-allo-inositol and (+/-)-3-O-acetyl-1,2:4,5-di-O-isopropylidene-6-O-methyl-allo-inositol.

The synthesis and conformational studies of (+/-)-3-O-acetyl-1,2:4,5-di-O-isopropylidene-allo-inositol and (+/-)-3-O-acetyl-1,2:4,5-di-O-isopropylidene-6-O-methyl-allo-inositol are described. Solid state conformations of the title compounds have been studied by solving their X-ray crystal structures. The inositol ring in both the compounds deviate considerably from the ideal chair conformation to flattened chair conformation in the solid state. Their conformations in solution were studied by the use of 1H NMR spectroscopy. These conformational analyses revealed that the title compounds adopt similar conformations in solid and solution states irrespective of the solvent polarity.

Alkenes↗
PubMed1997

A role for hydrolysis of inositol 1,4,5-trisphosphate in terminating the response to inositol 1,4,5-trisphosphate and to a flash of light in Limulus ventral photoreceptors.

Injection of inositol 1,4,5-trisphosphate (Ins 1,4,5-P3) into Limulus ventral photoreceptors produces excitation similar to that produced by light. One process which might contribute to rapid termination of the responses to Ins 1,4,5-P3 and to light is the hydrolysis of Ins 1,4,5-P3 by an InsP3-5-phosphatase to form inositol 1,4-bisphosphate. Inositol 2,4,5-trisphosphate (Ins 2,4,5-P3) is known to be less hydrolysable by the InsP3-5-phosphatase than is Ins 1,4,5-P3. Whereas ventral photoreceptors respond to an injection of Ins 1,4,5-P3 with a single wave of depolarization, the response to Ins 2,4,5-P3 is a burst of waves of depolarization. Our hypothesis is that it is the resistance to hydrolysis by the InsP3-5-phosphatase which accounts for the burst of waves produced by Ins 2,4,5-P3. To test this idea we injected ventral photoreceptors with Ins 1,4,5-P3 in the presence of the non-specific phosphatase inhibitors, vanadate and fluoride, which prolong the response to a flash of light in ventral photoreceptors (D.W. Corson, A. Fein, W.W. Walthall, J. Gen. Physiol. 82 (1983) 659-677). In the presence of fluoride or vanadate the response to Ins 1,4,5-P3 was composed of a burst of waves rather than a single wave of depolarization. We conclude that hydrolysis of Ins 1,4,5-P3 by the InsP3-5-phosphatase plays a role in terminating the ventral photoreceptors response to Ins 1,4,5-P3 and also to light.

Adaptation, Physiological↗