Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Polyphosphates”

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 1,225 records · Page 68Linked to original sources
PubMed1997

The interaction of diadenosine polyphosphates with P2x-receptors in the guinea-pig isolated vas deferens.

1. The site(s) at which diadenosine 5',5"'-P1,P4-tetraphosphate (AP4A) and diadenosine 5', 5"'-P1,P5-pentaphosphate (AP5A) act to evoke contraction of the guinea-pig isolated vas deferens was studied by use of a series of P2-receptor antagonists and the ecto-ATPase inhibitor 6-N,N-diethyl-D-beta,gamma-dibromomethyleneATP (ARL 67156). 2. Pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) (300 nM - 30 microM), suramin (3-100 microM) and pyridoxal-5'-phosphate (P-5-P) (3-1000 microM) inhibited contractions evoked by equi-effective concentrations of AP5A (3 microM), AP4A (30 microM) and alpha,beta-methyleneATP (alpha,beta-meATP) (1 microM), in a concentration-dependent manner and abolished them at the highest concentrations used. 3. PPADS was more potent than suramin, which in turn was more potent than P-5-P. PPADS inhibited AP5A, AP4A and alpha,beta-meATP with similar IC50 values. No significant difference was found between IC50 values for suramin against alpha,beta-meATP and AP5A or alpha,beta-meATP and AP4A, but suramin was more than 2.5 times more potent against AP4A than AP5A. P-5-P showed the same pattern of antagonism. 4. Desensitization of the P2xi-receptor by alpha,beta-meATP abolished contractions evoked by AP5A (3 microM) and AP4A (30 microM), but had no effect on those elicited by noradrenaline (100 microM). 5. ARL 67156 (100 microM) reversibly potentiated contractions evoked by AP4A (30 microM) by 61%, but caused a small, significant decrease in the mean response to AP5A (3 microM). 6. It is concluded that AP4A and AP5A act at the P2xi-receptor, or a site similar to the P2xi-receptor, to evoke contraction of the guinea-pig isolated vas deferens. Furthermore, the potency of AP4A, but not AP5A, appears to be inhibited by an ecto-enzyme which is sensitive to ARL 67156.

Adenosine Triphosphatases↗
PubMed1987

Homologous desensitization of substance-P-induced inositol polyphosphate formation in rat parotid acinar cells.

Maximal concentrations of substance P and methacholine induced a rapid increase in [3H]inositol trisphosphate ([3H]IP3) formation. After about 1 min, the [3H]IP3 in the substance-P-treated cells ceased to increase further, whereas in the methacholine-treated cells [3H]IP3 continued to increase. Addition of methacholine to the substance-P-treated cells caused a rapid increase in [3H]IP3, whereas a second addition of a 10-fold excess of substance P had no effect. Pretreatment of cells with substance P, followed by removal of the substance P by washing, resulted in a decreased response to a second application of substance P. A similar protocol involving pretreatment with methacholine had no effect on subsequent responsiveness to substance P. Analysis of [3H]substance P binding to substance-P-treated cells indicated that the number of receptors for substance P was decreased, but the affinity of the receptors for substance P was unaffected. After substance P pretreatment, a prolonged incubation (2 h) restored responsiveness of the cells to substance P, measured as [3H]IP3 formation, and restored the number of binding sites to control values. These findings indicate that, in the rat parotid gland, substance P induces a homologous desensitization of its receptor, which involves a slowly reversible down-regulation or sequestration of substance-P-binding sites.

Animals↗
PubMed1989

Accumulation of inositol polyphosphate isomers in agonist-stimulated cerebral-cortex slices. Comparison with metabolic profiles in cell-free preparations.

1. Basal and carbachol-stimulated accumulations of isomeric [3H]inositol mono-, bis-, tris- and tetrakis-phosphates were examined in rat cerebral-cortex slices labelled with myo-[2-3H]inositol. 2. In control samples the major [3H]inositol phosphates detected were co-eluted on h.p.l.c. with Ins(1)P, Ins(4)P (inositol 1- and 4-monophosphate respectively), Ins(1,4)P2 (inositol 1,4-bisphosphate), Ins(1,4,5)P3 (inositol 1,4,5-tris-phosphate) and Ins(1,3,4,5)P4 (inositol 1,3,4,5-tetrakisphosphate). 3. After stimulation to steady state with carbachol, accumulation of each of these products was markedly increased. 4. Agonist stimulation, however, also evoked much more dramatic increased accumulations of a second [3H]inositol trisphosphate, which was co-eluted on h.p.l.c. with authentic Ins(1,3,4)P3 (inositol 1,3,4-trisphosphate) and of three further [3H]inositol bisphosphates ([3H]InsP2(s]. 5. Examination of the latter by chemical degradation by periodate oxidation and/or h.p.l.c. allowed identification of these as [3H]Ins(1,3)P2, [3H]Ins(3,4)P2 and [3H]Ins(4,5)P2 (inositol 1,3-, 3,4- and 4,5-bisphosphates respectively), which respectively accounted for about 22%, 8% and 3% of total [3H]InsP2 in extracts from stimulated tissue slices. 6. By using a h.p.l.c. method which clearly resolves Ins(1,3,4,5)P4 and Ins(1,3,4,6)P4 (inositol 1,3,4,6-tetrakisphosphate), only the former isomer could be detected in extracts from either control or stimulated tissue slices. Similarly, [3H]inositol pentakis- and hexakis-phosphates were not detectable either in the presence or absence of carbachol under the radiolabelling conditions described. 7. The catabolism of [3H]Ins(1,4,5)P3 and [3H]Ins(1,3,4)P3 by cell-free preparations from cerebral cortex was also studied. 8. In the presence of Mg2+, [3H]Ins(1,4,5)P3 was specifically dephosphorylated via [3H]Ins(1,4)P2 and [3H]Ins(4)P to free [3H]inositol, whereas [3H]Ins(1,3,4)P3 was degraded via [3H]Ins(3,4)P2 and, to a lesser extent, via [3H]Ins(1,3)P2 to D- and/or L-[3H]Ins(1)P and [3H]inositol. 9. In the presence of EDTA, hydrolysis of [3H]Ins(1,4,5)P3 was greater than or equal to 95% inhibited, whereas [3H]Ins(1,3,4)P3 was still degraded, but yielded only a single [3H]InsP2 identified as [3H]Ins(1,3)P2. 10. The significance of these observations with cell-free preparations is discussed in relation to the proportions of the separate isomeric [3H]inositol phosphates measured in stimulated tissue slices.

Animals↗
PubMed1990

Product-precursor relationships amongst inositol polyphosphates. Incorporation of [32P]Pi into myo-inositol 1,3,4,6-tetrakisphosphate, myo-inositol 1,3,4,5-tetrakisphosphate, myo-inositol 3,4,5,6-tetrakisphosphate and myo-inositol 1,3,4,5,6-pentakisphosphate in intact avian erythrocytes.

Avian erythrocytes were incubated with myo-[3H]inositol for 6-7 h and with [32P]Pi for the final 50-90 min of this period. An acid extract was prepared from the prelabelled erythrocytes, and the specific radioactivities of the gamma-phosphate of ATP and of both the myo-inositol moieties (3H, d.p.m./nmol) and the individual phosphate groups (32P, d.p.m./nmol) of [3H]Ins[32P](1,3,4,6)P4,[3H]Ins[32P](1,3,4,5)P4, [3H]Ins[32P](3,4,5,6)P4 and [3H]Ins[32P](1,3,4,5,6)P5 were determined. The results provide direct confirmation that one of the cellular InsP4 isomers is Ins(1,3,4,5)P4 which is synthesized by sequential phosphorylation of the 1,4,5 and 3 substitution sites of the myo-Ins moiety, precisely as previously deduced [Batty, Nahorski & Irvine (1985) Biochem. J. 232, 211-215; Irvine, Letcher, Heslop & Berridge (1986) Nature (London) 320, 631-634]. This is compatible with the proposed synthetic route from PtdIns via PtdIns4P, PtdIns(4,5)P2 and Ins(1,4,5)P3. The data also suggest that, in avian erythrocytes, the principle precursor of Ins(1,3,4,5,6)P5 is Ins(3,4,5,6)P4. Furthermore, if the gamma- (and/or beta-) phosphate of ATP is the precursor of the phosphate moieties of Ins(3,4,5,6)P4, then this isomer must be derived from the phosphorylation of Ins(3,4,6)P3. If the gamma- (and/or beta-) phosphate of ATP similarly acts as the ultimate precursor to all of the phosphates of Ins(1,3,4,6)P4, then, in intact avian erythrocytes, the main precursor of Ins(1,3,4,6)P4 is Ins(1,4,6)P3. This contrasts with the expectation, based on results with cell-free systems, that Ins(1,3,4,6)P4 is synthesized by the direct phosphorylation of Ins(1,3,4)P3.

Adenosine Triphosphate↗
PubMed1992

Evidence for phosphatidylinositol hydrolysis in pancreatic islets stimulated with carbamoylcholine. Kinetic analysis of inositol polyphosphate metabolism.

Anion-exchange h.p.l.c. was used initially to analyse the products formed after addition of either [3H]Ins(1,3,4,5)P4 or [3H]Ins(1,4,5)P3 to homogenates of pancreatic islets. Metabolic routes similar to those of other tissues were established: dephosphorylation of Ins(1,4,5)P3 to Ins(1,4)P2 and then Ins4P; and sequential degradation of Ins(1,3,4,5)P4 to Ins(1,3,4)P3, Ins(3,4)P2 and Ins(3 or 1)P. In addition, there was a limited conversion of Ins(1,3,4)P3 into Ins(1,3)P2. After stimulation of [3H]inositol-prelabelled islets with the muscarinic-receptor agonist carbamoylcholine (carbachol), there was a rapid (10 s) increase in Ins(1,4,5)P3, Ins(1,3,4)P3, Ins(1,4)P2 and Ins4P. In the presence of 10 mM-LiCl, Ins1P was also significantly increased (P less than 0.05) by 5 s, before any increase in Ins4P (10 s), Ins(1,3)P2 (60 s) or Ins(3,4)P2. When carbachol was displaced with atropine, after 1 h pre-stimulation, the maximal decreases in Ins(1,4,5)P3 and Ins1P from the stimulated steady state (5 s) clearly preceded those of the other metabolites. These declines were used to calculate the turnover times and rate of metabolic flux through the various inositol phosphates. These experiments confirmed the relatively minor importance of the Ins(1,3)P2 pathway (less than 10% of the total flux) and demonstrated that Ins(1,4,5)P3 removal was evenly distributed through the Ins(1,4)P2 and Ins(1,3,4,5)P4 routes. They also established that flux through Ins1P was 8-fold greater than that through Ins(1,4,5)P3, indicating that the former could not have been derived from PtdInsP2 hydrolysis. Similarly, in islets pretreated with neomycin, which binds to PtdInsP2 with greater affinity than to PtdIns, the increase in Ins1P caused by 1 min stimulation with carbachol was not affected, despite virtual abolition of the increase in Ins4P, and an overall inhibition of PtdInsP2 hydrolysis by 67%. The results indicate that, in addition to PtdInsP2 breakdown, carbachol also promotes a rapid PtdIns hydrolysis which becomes increasingly predominant with prolonged stimulation.

Animals↗
PubMed2003

Morton Medal Lecture. New insights into the roles of phosphoinositides and inositol polyphosphates in yeast.

During the past half century, we have progressed from simply viewing myo -inositol-containing glycerophospholipids as quantitatively minor membrane constituents to the present, very striking, situation in which more and more important cellular functions are being assigned to a plethora of phosphorylated derivatives of inositol and phosphatidylinositol. Two such examples are discussed briefly: the activation by environmental stresses of the single phosphoinositidase C of yeast, which is related to the phospholipase C delta s of other eukaryotes, and the involvement of PtdIns(3,5) P (2) in endomembrane trafficking.

Enzyme Activation↗
PubMed1999

Inositol polyphosphate-mediated iron transport in Pseudomonas aeruginosa.

It has previously been shown that myo-inositol hexakisphosphate (myo-InsP6) mediates iron transport into Pseudomonas aeruginosa and overcomes iron-dependent growth inhibition. In this study, the iron transport properties of myo-inositol trisphosphate and tetrakisphosphate regio-isomers were studied. Pseudomonas aeruginosa accumulated iron (III) at similar rates whether complexed with myo-Ins(1,2,3)P3 or myo-InsP6. Iron accumulation from other compounds, notably D/L myo-Ins(1,2,4,5)P4 and another inositol trisphosphate regio-isomer, D-myo-Ins(1,4,5)P3, was dramatically increased. Iron transport profiles from myo-InsP6 into mutants lacking the outer membrane porins oprF, oprD and oprP were similar to the wild-type, indicating that these porins are not involved in the transport process. The rates of reduction of iron (III) to iron (II) complexed to any of the compounds by a Ps. aeruginosa cell lysate were similar, suggesting that a reductive mechanism is not the rate-determining step.

Biological Transport↗
PubMed2001

Mammalian inositol polyphosphate multikinase synthesizes inositol 1,4,5-trisphosphate and an inositol pyrophosphate.

Using a consensus sequence in inositol phosphate kinase, we have identified and cloned a 44-kDa mammalian inositol phosphate kinase with broader catalytic capacities than any other member of the family and which we designate mammalian inositol phosphate multikinase (mIPMK). By phosphorylating inositol 4,5-bisphosphate, mIPMK provides an alternative biosynthesis for inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)]. mIPMK also can form the pyrophosphate disphosphoinositol tetrakisphosphate (PP-InsP(4)) from InsP(5). Additionally, mIPMK forms InsP(4) from Ins(1,4,5)P(3) and InsP(5) from Ins(1,3,4,5)P(4).

Amino Acid Sequence↗