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PubMed2000

Separation of diadenosine polyphosphates by capillary electrophoresis.

The influence of buffer composition and pH on the electrophoretic behavior of diadenosine polyphosphates with a phosphate chain ranging from two to five phosphate groups has been examined. The electrophoretic mobility in carbonate buffer increases according to the number of phosphates, whereas in borate buffer the mobility changes in an irregular way as a function of pH. This finding can be rationalized by a well-known interaction of borate with ribose rings, which modifies the charge and the hydrodynamic radius of each diadenosine polyphosphate in a different way. Our study shows that the best separation of diadenosine polyphosphates can be achieved at the highest pH values of the range examined both in borate and carbonate buffers.

Borates↗
PubMed1996

The diadenosine polyphosphate receptors: P2D purinoceptors.

Diadenosine polyphosphates-Ap4A, Ap5A and Ap6A-are co-stored in neurosecretory vesicles together with ATP and aminergic compounds. They are released from neural cells and synaptic terminals in a Ca(2+)-dependent process. Ligand binding and displacement experiments carried out with [3H]Ap4A on isolated chromaffin cells and synaptosomal preparations result in curvilinear Scatchard plots with Kd values close to 0.1 nM for the high-affinity binding sites. Displacement curves with two steps are obtained for homologous and heterologous nucleotide ligands; the lowest-affinity step exhibits Ki values in the micromolar range for ApnA compounds. The high-affinity binding sites were named P2D purinoceptors on the basis of their binding characteristics. Single-cell studies in neurochromaffin cells indicate the presence of P2X purinoceptors in noradrenergic cells that do not respond to Ap4A and in which noradrenaline secretion can be induced by influx of extracellular Ca2+. P2Y receptors that respond to ATP analogues and ApnAs are present in endothelial cells from adrenal medulla. Those cells that express P2U purinoceptors are unresponsive to ApnAs. Ectodiadenosine polyphosphate hydrolases with Km values of 0.3 to 2 microM are present in both neural and endothelial cells from adrenal medulla. In midbrain synaptic terminals diadenosine polyphosphates induce Ca2+ entry from the extracellular medium. The fact that the synaptic response is not cross-desensitized by ATP and its non-hydrolysable analogues, the non-blocking effect of suramin, and the differential effect of Ca2+ channel blockers, together suggest that there are different receptors for nucleotides and dinucleotides in rat brain synaptosomes, which we have called P4 purinoceptors on the basis of functional studies.

Adrenal Medulla↗
PubMed1995

Polyphosphate accumulation among denitrifying bacteria in activated sludge.

Bacterial polyphosphate accumulation and denitrification are important processes in biological removal of nutrients from wastewater. It has been suggested that phosphorus accumulators are able to denitrify. However, the bacteria known as the most important phosphorus accumulators, belonging to the genus Acinetobacter are generally not known to denitrify. To clarify how commonly both physiological traits are present in the same organism, we screened 165 isolates from activated sludge and wastewater for their ability to denitrify, and the ability of the denitrifying isolates to accumulate polyphosphate. Of the 165 isolates, 149 were from acetate mineral medium (87 of these identified as Acinetobacter by the API 20 NE identification system) and 16 were from nutrient broth and nitrate medium. Only 15 of 165 isolates tested showed true respiratory denitrification activity. In the presence of acetylene they converted more than 80% of 5mM NO3- to N2O in 6 days. None of the Acinetobacter isolates were among the 15 respiratory denitrifiers. The denitrifying isolates were identified as species of Pseudomonas, Agrobacterium, Pasteurella, Sphingomonas or could not be identified by the API 20 NE identification system. According to the BIOLOG identification system the denitrifiers were species of Pseudomonas, Hydrogenophaga, Citrobacter, Xanthomonas or they could not be identified. The ability of confirmed denitrifiers to accumulate phosphate was measured in experiments where cells pregrown under phosphorus limitation were exposed to phosphate (8 mg P/L) under aerobic conditions. The rates of excess phosphate uptake varied from 0.3 to more than 23 mg P/g dry matter/h. Rates for four isolates were higher than those reported for Acinetobacter strains. These results show that polyphosphate accumulation and denitrification in activated sludge can be carried out by the same organisms.

Journal Article↗
PubMed1996

Biosynthesis of the endogenous cyclic adenosine monophosphate (AMP) antagonist, prostaglandylinositol cyclic phosphate (cyclic PIP), from prostaglandin E and activated inositol polyphosphate in rat liver plasma membranes.

The endogenous cyclic adenosine monophosphate (AMP) antagonist, cyclic PIP, has been identified as a prostaglandylinositol cyclic phosphate. It inhibits protein kinase A 100% and activates protein serine phosphatase about sevenfold. It is biosynthesized by an enzyme of the plasma membrane when the assay mixture contains adenosine triphosphate (ATP), Mg2+, prostaglandin E and a novel inositol polyphosphate, which cannot be substituted by commercially available inositol phosphates. This novel inositol polyphosphate is a very labile compound. On anion exchange chromatography it elutes in the range of ATP, which may indicate the presence of three phosphate groups. It adsorbs on charcoal, which suggests the presence of a hydrophobic component, possibly a guanosine. Pyrophosphates obtained from inositol 1,4- and inositol 2,4-bisphosphate are accepted by cyclic PIP synthetase for the synthesis of cyclic PIP. The biosynthesis is characterized by enzyme kinetic parameters like dependence on time, enzyme and substrate concentration. The pH optimum of the enzyme is in the range 7.5-8. The enzyme functions optimally with prostaglandin E and poorly with prostaglandin A as the substrate. The presence of fluoride in the assay causes a three- to fourfold increase in cyclic PIP synthesis, which may be correlated with activation via G proteins. These data support previous reports on the chemical structure and action of cyclic PIP. With respect to the possible isomers of cyclic PIP, these indicate that it is most likely the C4-hydroxyl group of the inositol which binds the C15-hydroxyl group of prostaglandin E. A model of hormone-stimulated synthesis of cyclic PIP is proposed: phospholipase A2 and phospholipase C, activated by G proteins upon alpha-adrenergic stimulation, liberate either unsaturated fatty acids or inositol phosphates, which are transformed to prostaglandins and to novel inositol polyphosphate with an energy-rich bond. The cyclic PIP synthetase combines these two substrates to cyclic PIP.

Animals↗
PubMed1977

[The behavior of polyphosphates during production and storage of long keeping milk products (author's transl)].

Polyphosphates added as stabilizers in the production process if liquid sterilized milk products are completely hydrolyzed to mono- and diphosphates. The diphosphate is further hydrolyzed during storage of the products. The extent of hydrolysis of diphosphate depends upon the processing conditions and may vary from production to production. During spray-drying of milk, the polyphosphates added are only partially hydrolyzed; further degradation of the polyphosphates takes place during storage.

Animals↗
PubMed1976

Formation of nucleoside 5'-polyphosphates under potentially prebiological conditions.

Aqueous solutions of linear inorganic polyphosphates incubated in presence of Mg ions depolymerize to give trimetaphosphate. The presence of a nucleoside 5'-phosphate has little influence upon the reaction. Drying the products obtained by incubating a linear polyphosphate with Mg ions in the presence of a nucleoside 5'-phosphate yields nucleoside 5'-polyphosphates. The prebiological relevance of the reactions is discussed.

Chemical Phenomena↗
PubMed1996

Diadenosine polyphosphate-induced inhibition of cardiac KATP channels: operative state-dependent regulation by a nucleoside diphosphate.

It has been proposed that the regulatory action of mononucleotides, such as ATP and UDP, on cardiac ATP-sensitive K+ (KATP) channels is determined by the state of the channel. Recently, dinucleotides, such as diadenosine tetraphosphate (Ap4A) and diadenosine pentaphosphate (Ap5A), have been recognized as novel intracellular ligands of cardiac KATP channels. However, it is not known whether the state of KATP channels also determines the response of the channel to dinucleotides. Therefore, we examined the action of diadenosine polyphosphates on KATP channel activity during different operative channel states, using the inside-out patch clamp technique applied to patches excised from guinea-pig ventricular myocytes. Spontaneous openings of KATP channels (or operative condition 1) were inhibited by Ap4A and Ap5A. Addition of UDP, which on its own did not affect spontaneous openings of KATP channels, prevented Ap4A and Ap5A to inhibit spontaneous KATP channel activity. In contrast, following "run-down" of spontaneous channel activity, UDP induced KATP channel openings (or operative condition 2), but could no longer antagonize the inhibitory effect of Ap4A and Ap5A. We conclude that the inhibitory action of diadenosine polyphosphates on KATP channels can be blocked by UDP only when KATP channels are in operative condition 1, but not in operative condition 2. Thus, the operative condition of KATP channels determines the UDP-mediated regulation of the diadenosine polyphosphate-dependent inhibitory channel gating. This finding further suggests that the operative state of the cardiac KATP channel protein is a critical determinant of the regulatory action of an intracellular ligand.

Animals↗
PubMed2000

Effects of phytate and pyrophosphate on brushite and hydroxyapatite crystallization. Comparison with the action of other polyphosphates.

This is a comparative study of the effects of phytate and pyrophosphate and other polyphosphates on the crystallization of hydroxyapatite and brushite, the most frequent calcium phosphates involved in calcium oxalate urolithiasis. Brushite and hydroxyapatite crystal formation was studied in synthetic urine, through kinetic-turbidimetric measurements that allowed evaluation of the inhibitory effects on crystallization of insoluble salts. The effectiveness in preventing brushite crystallization decreases in the sequence phytate > polyphosphate > EDTPO > etidronate > pyrophosphate > triphosphate > medronate; whereas the order of effectiveness in preventing hydroxyapatite crystallization was EDTPO > etidronate = pyrophosphate > triphosphate > medronate > polyphosphate > phytate. Phytate, a natural inhibitor in urine, most effectively blocked brushite precipitation (1.21x10(-5) M prevented crystallization during time periods of at least 1 h), and pyrophosphate was the natural inhibitor that most effectively blocked hydroxyapatite precipitation (2.87x10(-6) M prevented crystallization during time periods of at least 1 h). This demonstrates that low excretion of these substances would pose a risk of renal lithiasis.

Calcium Phosphates↗
PubMed1975

Detection of acute myocardial infarction by technetium-99m polyphosphate.

Experimental work has shown that technetium-99m (99mTc) pyrophosphate accumulates in recently infarcted myocardium and can be detected by external imaging techniques. Twenty-two 99mTc polyphosphate myocardial studies were performed in 17 patients (in 3 after cardiac surgery) 3 to 20 days after myocardial infarction. Seventeen myocardial studies were performed in 17 control patients (in 6 after cardiac surgery). Twenty millicuries of 99mTc polyphosphate was injected intravenously 60 to 120 minutes prior to gamma camera imaging in several views. Myocardial images were processed by the Gamma-11 computer system using standardized background subtraction and contrast enhancement. Results of 16 myocardial studies performed 4 to 20 days after transmural myocardial infarction in 12 patients were positive in 13 instances and questionable in 1. The location of the myocardial infarction by imaging corresponded to location by standard electrocardiograhic criteria in 8 of the 10 patients with positive findings. In five patients with nontransmural myocardial infarction, results of myocardial imaging were positive in two, questionable in one and normal in one. In one patient with questionable findings results were normal when imaging was repeated 16 days after nontransmural myocardial infarction. Results of 17 control myocardial imaging studies were normal in 16 and questionable in 1. Therefore, 99mTc polyphosphate myocardial imaging appears promising in the detection and location of transmural myocardial infarction. Its accuracy in detecting nontransmural myocardial infarction may be increased with greater experience and development of sophisticated digital analysis techniques. The method may prove useful in clinical situations such as cardiac surgery in which standard diagnostic aids are difficult to interpret.

Acute Disease↗
PubMed1996

Diadenosine polyphosphates regulate cytosolic calcium in human fibroblast cells by interaction with P2x purinoceptors coupled to phospholipase C.

The effects of diadenosine pentaphosphate (AP5A), and diadenosine hexaphosphate (AP6A) on the cytosolic-free Ca2+ concentration ([Ca2+]i) were evaluated in cultured human fibroblast cells (HF cells) using the fluorescent dye technique. AP5A, and AP6A concentration-dependently increased [Ca2+]i in HF cells. The addition of 10 mumol/1 AP5A and AP6A significantly increased [Ca2+]i in HF cells from 71 +/- 3 nmol/1 (n = 184) to 241 +/- 39 nmol/1 (n = 11; P < 0.001 compared to resting value) and to 227 +/- 26 nmol/1 (n = 23; P < 0.001), respectively. The purinoceptor P2 blockers, suramin and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), inhibited the diadenosine polyphophate-induced [Ca2+]i increase, whereas the P2y purinoceptor blocker, reactive blue, had no effect. Adenosinetriphosphate (ATP) and the P2x agonist, alpha 1 beta-methylene-ATP also significantly increased [Ca2+]i in HF cells, whereas the P2y agonist methylthio-ATP showed only a small [Ca2+]i response. Diadenosine polyphosphates mainly induced transplasmamembrane Ca2+ influx as was confirmed by experiments in the absence of extracellular Ca2+ or by manganese quenching studies. Organic (verapamil) and inorganic Ca2+ channel blockers (NiCI2) significantly reduced the AP6A induced transplasmamembrane Ca2+ influx. The inhibitor of phosphatidylcholine-specific phospholipase C, D609, significantly reduced the effect of diadenosine polyphosphates on [Ca2+]i in HF cells. It is concluded that diadenosine polyphosphates regulate transplasmamembrane Ca2+ influx after occupation of P2x receptors via activation of phosphatidylcholine-specific phospholipase C and hence of voltage-operated Ca2+ channels.

Bridged-Ring Compounds↗
PubMed2005

Spectroscopic investigation of a new hybrid glass formed by the interaction between croconate ion and calcium polyphosphate.

In this work, a new organic-inorganic hybrid material has been synthesized by the incorporation of croconate ion into a calcium polyphosphate coacervate. The hybrid so obtained was characterized by means of electronic and vibrational spectroscopies. The material is a homogeneous mixture described by a structural model, which includes helical chains of polyphosphate ions, where the calcium ion occupies the internal vacancies of the structure. The croconate ion appears to be occupying the regions outside the polymeric structure, surrounded by several water molecules. The electronic spectrum of the incorporated material shows a broad band peaking at the same wavelength region (363 nm) observed for the aqueous solution of croconate ion, and manifesting the Jahn-Teller effect as evidenced by the doublet structure of the band. The infrared spectrum is widely dominated by the absorption bands of the polyphosphate ion and the appearance of the carbonyl stretching band at ca. 1550 cm(-1) indicates the presence of croconate ion incorporated in the structure. The Raman spectrum of the material shows several vibrational bands related to the oxocarbon moiety; most of them are shifted in comparison with the free ion. These shifts can be understood in terms of strong hydrogen bonding interactions between water molecules and the oxocarbon moiety. The low temperature methodology proposed here can be well used in the preparation of new phosphate glasses containing organic moieties opening the route to an entirely new class of hybrid glasses.

Anions↗
PubMed2003

Crystallization and characterization of polyphosphate kinase from Escherichia coli.

Linear polyphosphate chains have been found to play a key role in bacterial responses to stresses and nutritional depletion, and are necessary for host infection of various pathogens. Polyphosphate kinase (PPK) is a critical enzyme responsible for polyphosphate synthesis in bacteria. PPK knockout mutations in several Gram-negative pathogens identify PPK as an ideal drug target for the development of a new class of antibacterial drugs. To reveal the catalytic mechanism and provide a structural basis for drug discovery, we have purified and crystallized full-length Escherichia coli PPK and its complex with AMP-PNP. The crystals diffract to a resolution of 2.5A and belong to the space group P4(2)2(1)2 with unit-cell parameters a=152.0, b=152.0, and c=150.0 A. Crystal structure of PPK is being determined by the Se-Met MAD experiment.

Adenylyl Imidodiphosphate↗
PubMed1999

Role of synaptotagmin, a Ca2+ and inositol polyphosphate binding protein, in neurotransmitter release and neurite outgrowth.

Synaptotagmin I (or II), a possible Ca(2+)-sensor of synaptic vesicles, has two functionally distinct C2 domains: the C2A domain binds Ca2+ and the C2B domain binds inositol high polyphosphates (IP4, IP5, and IP6). Ca(2+)-regulated exocytosis of secretory vesicles is proposed to be activated by Ca2+ binding to the C2A domain and inhibited by inositol polyphosphate binding to the C2B domain. Synaptotagmins now constitute a large family and are thought to be involved in both regulated and constitutive vesicular trafficking. They are classified from their distribution as neuronal (synaptotagmin I-V, X, and XI) and the ubiquitous type (synaptotagmin VI-IX). Among them, synaptotagmins III, V, VI and X are deficient in IP4 binding activity due to the amino acid substitutions in the C-terminal region of the C2B domain, suggesting that these isoforms can work for vesicular trafficking even in the presence of inositol high polyphosphates. Synaptotagmin I is also known to be present in neuronal growth cone vesicles. Antibody against the C2A domain (anti-C2A) that inhibits Ca(2+)-regulated exocytosis also blocked neurite outgrowth of the chick dorsal root ganglion (DRG) neuron, suggesting that Ca(2+)-dependent synaptotagmin activation is also crucial for neurite outgrowth.

Amino Acid Sequence↗
PubMed2002

Potent desensitization of human P2X3 receptors by diadenosine polyphosphates.

In this study, the receptor desensitizing effects of diadenosine polyphosphates at recombinant human P2X3 (hP2X3) receptors were examined. Administration of Ap3A, Ap4A, Ap5A or Ap6A inhibited the hP2X3 receptor-mediated response to a subsequent application of 3 muM alphabeta-methyleneATP (alphabeta-meATP), in a concentration-dependent manner, with IC50 values 2707, 42, 59 and 46 nM, respectively. These agonists did not desensitize alphabeta-meATP responses mediated by the slowly desensitizing heteromeric human P2X2/3 receptor. hP2X3 receptor desensitization was reversible and was not observed following the increase in intracellular Ca2+ levels produced by carbachol. A similar pattern of desensitization evoked by Ap5A was also observed using electrophysiological recordings of Xenopus oocytes expressing hP2X3 receptors. These data demonstrate that diadenosine polyphosphates, found endogenously in the central nervous system, can readily desensitize hP2X3 receptors at nanomolar concentrations that are 10-fold lower than are required to produce agonist-induced receptor activation. Thus, P2X3 receptor desensitization by diadenosine polyphosphates may provide an important modulatory mechanism of P2X3 receptor activation in vivo.

Adenosine Triphosphate↗
PubMed2003

pH opposite effects on synthesis of dinucleoside polyphosphates and on oxidation reactions catalyzed by firefly luciferase.

Previous results have shown that an oxidizing product of firefly luciferin, dehydroluciferyl-adenylate, is the main intermediate in the process of synthesis of dinucleoside polyphosphates catalyzed by firefly luciferase (EC 1.13.12.7). However, we have found that the pH effects on the luciferase oxidizing processes and on the synthesis of dinucleoside polyphosphate are opposite: acidic assay media enhance the synthesis of dinucleoside polyphosphate and inhibit the oxidizing processes. The reason for this apparent contradiction lies on the activation effect of low pH on the adenylate transfer reaction from dehydroluciferyl-adenylate to the acceptor nucleotide.

Animals↗
PubMedDate not supplied

Specific and nonspecific enzymes involved in the catabolism of mononucleoside and dinucleoside polyphosphates.

This review concerns enzymes that can degrade nucleoside 5'-tetra- and pentaphosphates (p(4)N and p(5)N) and those that can degrade various dinucleoside polyphosphates (Np(3-6)N'). Most of these enzymes are hydrolases, and they occur in all types of organisms. Certain fungi and protozoa also possess specific Np(n)N' phosphorylases. Specific p(4)N hydrolases have been demonstrated in mammals and in plants. In yeast, p(4)N and p(5)N are hydrolyzed by exopolyphosphatases. Among other hydrolases that can degrade these minor mononucleotides are phosphatases, apyrase, and (asymmetrical) Np(4)N' hydrolase, as well as the nonspecific adenylate deaminase. Np(n)N's are good substrates for Type I phosphodiesterases and nucleotide pyrophosphatases, and diadenosine polyphosphates are easily deaminated to diinosine polyphosphates by nonspecific adenylate deaminases. Specific Np(3)N' hydrolases occur in both prokaryotes and eukaryotes. Interestingly, the human fragile histidine triad (Fhit) tumor suppressor protein appears to be a typical Np(3)N' hydrolase. Among the specific Np(4)N' hydrolases are asymmetrically cleaving ones, which are typical of higher eukaryotes, and symmetrically cleaving enzymes found in Physarum polycephalum and in many bacteria. An enzyme that hydrolyzes both diadenosine tetraphosphate and diadenosine triphosphate has been found in the fission yeast Schizosaccharomyces pombe. Its amino acid sequence is similar to that of the human Fhit/Np(3)N' hydrolase. Very recently, a typical (asymmetrical) Np(4)N' hydrolase has been demonstrated for the first time in a bacterium-the pathogenic Bartonella bacilliformis. Another novelty is the discovery of diadenosine 5', 5"'-P(1),P 6-hexaphosphate hydrolases in budding and fission yeasts and in mammalian cells. These enzymes and the (asymmetrical) Np(4)N' hydrolases have the amino acid motif typical of the MutT (or Nudix hydrolase) family. In contrast, the Schizosaccharomyces pombe Ap(4)A/Ap(3)A hydrolase, the human Fhit protein, and the yeast Np(n)N' phosphorylases belong to a superfamily GAFH, which includes the histidine triad proteins.

Animals↗
PubMedDate not supplied

Synthesis of dinucleoside polyphosphates catalyzed by firefly luciferase and several ligases.

The findings presented here originally arose from the suggestion that the synthesis of dinucleoside polyphosphates (Np(n)N) may be a general process involving enzyme ligases catalyzing the transfer of a nucleotidyl moiety via nucleotidyl-containing intermediates, with release of pyrophosphate. Within this context, the characteristics of the following enzymes are presented. Firefly luciferase (EC 1.12. 13.7), an oxidoreductase with characteristics of a ligase, synthesizes a variety of (di)nucleoside polyphosphates with four or more inner phosphates. The discrepancy between the kinetics of light production and that of Np(n)N synthesis led to the finding that E*L-AMP (L = dehydroluciferin), formed from the E*LH(2)-AMP complex (LH(2) = luciferin) shortly after the onset of the reaction, was the main intermediate in the synthesis of (di)nucleoside polyphosphates. Acetyl-CoA synthetase (EC 6.2.1.1) and acyl-CoA synthetase (EC 6.2.1. 8) are ligases that synthesize p(4)A from ATP and P(3) and, to a lesser extent, Np(n)N. T4 DNA ligase (EC 6.5.1.1) and T4 RNA ligase (EC 6.5.1.3) catalyze the synthesis of Np(n)N through the formation of an E-AMP complex with liberation of pyrophosphate. DNA is an inhibitor of the synthesis of Np(n)N and conversely, P(3) or nucleoside triphosphates inhibit the ligation of a single-strand break in duplex DNA catalyzed by T4 DNA ligase, which could have therapeutic implications. The synthesis of Np(n)N catalyzed by T4 RNA ligase is inhibited by nucleoside 3'(2'),5'-bisphosphates. Reverse transcriptase (EC 2.7.7.49), although not a ligase, catalyzes, as reported by others, the synthesis of Np(n)ddN in the process of removing a chain termination residue at the 3'-OH end of a growing DNA chain.

Acetate-CoA Ligase↗
PubMed1997

Diadenosine polyphosphates' action on calcium and vessel contraction.

The effects of the endogenous, platelet-derived vasoactive compounds, diadenosine tetraphosphate (AP4A), diadenosine pentaphosphate (AP5A), and diadenosine hexaphosphate (AP6A) on the vasoconstriction of isolated rat renal resistance vessels and rat aortic strips were measured using a vessel myograph. In addition, the effects of AP4A, AP5A, and AP6A on the cytosolic free calcium concentration ([Ca2+]i) were evaluated in cultured rat vascular smooth muscle cells (VSMC) using the fluorescent dye technique. Diadenosine polyphosphates dose-dependently increased the force of renal resistance vessels and isolated aortic strips. The administration of 10 mumol/L AP4A, AP5A, or AP6A significantly increased the force of isolated renal resistance vessels by 3.48+/-0.43 mN (n = 8), 2.14+/-0.40 mN (n = 12), or 2.70+/-0.31 mN (n = 11, each P < .01 compared with resting tension), respectively. The administration of 10 micromol/L AP4A, AP5A, or AP6A significantly increased the force of isolated aortic strips by 2.45+/-0.97 mNewton (n = 10), 2.70+/- 0.30 mN (n = 6), or 1.48+/-0.20 mN (each P < .01 compared with resting tension), respectively. The administration of 10 micromol/L AP4A, AP5A, or AP6A significantly increased [Ca2+]i in VSMC to a peak concentration of 314+/-60 nmol/L (n = 6), 247+/-25 nmol/L (n = 15), or 332+/-100 nmol/L (n = 5), respectively (each P < .01 compared with resting value). Both the diadenosine polyphosphate-induced vasoconstriction and [Ca2+]i increase was significantly reduced in the absence of extracellular calcium or after administration of a specific inhibitor of P2 purinoceptors. It is concluded that diadenosine polyphosphates increase [Ca2+]i and hence cause vessel constriction.

Animals↗