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PubMed2000

Biochemical evidence for an ecto alkaline phosphodiesterase I in human airways.

Because dinucleotides are signaling molecules that can interact with cell surface receptors and regulate the rate of mucociliary clearance in lungs, we studied their metabolism by using human airway epithelial cells. A membrane-bound enzyme was detected on the mucosal surface of polarized epithelia that metabolized dinucleotides with a broad substrate specificity (diadenosine polyphosphates and diuridine polyphosphates [Up(n)U], n = 2 to 6). The enzymatic reaction yielded nucleoside monophosphates (NMP) and Np(n)(-)(1) (N = A or U), and was inhibited by nucleoside 5'-triphosphates (alpha,betamet adenosine triphosphate [ATP] > ATP >/= uridine triphosphate > guanidine triphosphate > cytidine triphosphate). The apparent Michaelis constant (K(m,app)) and apparent maximal velocity (V(max,app)) for [(3)H]Up(4)U were 22 +/- 4 microM and 0.24 +/- 0.05 nmoles. min(-)(1). cm(-)(2), respectively. Thymidine 5'-monophosphate p-nitrophenyl ester and adenosine diphosphate (ADP)- ribose, substrates of ecto alkaline phosphodiesterase I (PDE I) activities, were also hydrolyzed by the apical surface of airway epithelia. ADP-ribose competed with [(3)H]Up(4)U, with a K(i) of 23 +/- 3 microM. The metabolism of ADP-ribose and Ap(4)A was not affected by inhibitors of cyclic nucleotide phosphodiesterases (3-isobutyl-1-methylxanthine, Ro 20-1724, and 1,3-dipropyl-8-p-sulfophenylxanthine), but similarly inhibited by fluoride and N-ethylmaleimide. These results suggest that a PDE I is responsible for the hydrolysis of extracellular dinucleotides in human airways. The wide substrate specificity of PDE I suggests that it may be involved in several signaling events on the luminal surface of airway epithelia, including purinoceptor activation and cell surface protein ribosylation.

Acid Anhydride Hydrolases↗
PubMed1981

Visualization of nucleolar substructure in cultured human fibroblasts by magnesium-activated adenosine triphosphatase reaction.

Discrete sites of adenosine triphosphatase (ATPase) activity were demonstrated within the nucleoli of unfixed cultured human fibroblasts (IMR90, VA13, and AG2804 cells) by an adaptation, for electron microscopic cyto-chemistry, of Wachstein and Meisel's lead nitrate method. The majority of nucleoli contained more than one ATPase-positive region, but the total ATPase-positive material appeared to occupy only a minor portion of the nucleolar volume. These regions were roughly spherical with an irregular contour, and at times appeared to be components of perinucleolar chromatin or to be located adjacent to nucleolar interstices. The distribution of these regions within the nucleolus and their segregation by actinomycin D suggested that the ATPase-positive regions correspond to the fibrillar centers, which represent nucleolar organizer regions. The cytochemically demonstrable nucleolar ATPase was strictly dependent on the presence of divalent cations. Optimal reactions was seen at 5 mM Mg2+, but near optimal activity was obtained with lower concentrations of Mg2+ in the presence of Ca2+. Calcium alone and Mn2+ alone produced suboptimal reaction. Studies with different nucleoside phosphates as reaction substrates showed that the enzyme is specific for adenosine derivatives, ATP and dATP being equally good substrates. Guanosine triphosphate, cytidine triphosphate, uridine triphosphate, and d-thymidine triphosphate were ineffective as substrates, as were nucleoside mono- and diphosphates and other phosphate esters tested. It is suggested that the cytochemical ATPase reaction visualized the regions of the nucleolus in which ribosomal DNA of intranucleolar chromatin is undergoing conformational alterations.

Adenosine Triphosphatases↗
PubMed1985

Mechanism of synergy between N-phosphonacetyl-L-aspartate and dipyridamole in a human ovarian carcinoma cell line.

Previous results from our laboratory have shown that the nucleoside transport inhibitor dipyridamole (DP) markedly augmented both the in vitro and in vivo activities of the pyrimidine antimetabolite N-phosphonacetyl-L-aspartate (PALA). In a human ovarian carcinoma cell line (2008), DP increased the activity of PALA by 1 to 2 logs in growth rate and clonogenic assays while exhibiting no cytotoxicity of its own. The concentration of DP used (1 microM) in these assays resulted in over 80% reduction in uridine uptake in the 2008 cells at the end of 1 h. The activity of PALA and PALA plus DP was completely antagonized by the addition of exogenous uridine in a dose-dependent manner. Addition of other nucleosides to concentrations as high as 1000 microM failed to rescue the ovarian cells from the drug combination, and combining two nucleosides together did not antagonize PALA and PALA plus DP activity to any greater extent. Cellular nucleotide pool analysis by anion-exchange high-performance liquid chromatography revealed that dipyridamole further reduced the already depressed uridine triphosphate and cytidine triphosphate pools of cells exposed to PALA, while the guanosine triphosphate pool was slightly elevated. Uridine supplementation resulted in partial replenishment of the uridine triphosphate and cytidine triphosphate pools, but the absolute levels remained below control values. The acute drug-induced changes in nucleotide pools in 2008 xenografts growing in athymic mice paralleled those observed in vitro. Evidence presented here supports the ability of DP to potentiate PALA activity against a human ovarian carcinoma cell line. The mechanism of synergy relates to the inhibition of pyrimidine salvage in the tumor cells via the blockade of uridine uptake.

Antineoplastic Agents↗
PubMed1983

Ribonucleotide content of mononuclear cells from normal subjects and patients with chronic lymphocytic leukemia: increased nicotinamide adenine dinucleotide concentration in chronic lymphocytic leukemia lymphocytes.

The ribonucleotide content of lymphocytes obtained from normal subjects and patients with chronic lymphocytic leukemia (CLL) was determined by means of high-performance liquid chromatography. The levels of normal B- and T-cells were compared to each other as well as those of their CLL counterparts. Unfractionated CLL lymphocytes, predominantly B-cells, had significantly lower levels of adenosine-5'-triphosphate, cytidine-5'-triphosphate, uridine-5'-triphosphate, cytidine-5'-diphosphate, and guanosine-5'-phosphate, while the concentration of nicotinamide-adenine dinucleotide was significantly higher than in normal unfractionated lymphocytes which consisted mainly of T-cells. For enriched populations: (a) CLL B-cells had much lower adenosine-5'-triphosphate (3439 versus 5689) (pmol/1 X 10(7) cells), cytidine-5'-triphosphate (107 versus 313), guanosine-5'-triphosphate (462 versus 978), and uridine-5'-triphosphate (633 versus 1214) than normal B-cells; (b) CLL T-enriched subpopulations had significantly lower ribonucleoside triphosphates, adenosine-5'-triphosphate (3217 versus 5468), cytidine-5'-triphosphate (119 versus 209), guanosine-5'-triphosphate (422 versus 826), and uridine-5'-triphosphate (504 versus 969) than normal T-cells. The lower ribonucleoside triphosphate levels found in unfractionated CLL lymphocytes, therefore, are the result of differences between the CLL and normal B-cells as well as between CLL and normal T-cells. These findings establish a framework for studying the reasons underlying the decreased ribonucleoside triphosphate levels in unfractionated CLL lymphocytes. T-helper and T-suppressor lymphocytes showed similar ribonucleotide patterns. Nucleoside and base levels were significantly higher in normal monocytes than in normal lymphocytes. The only compound found to be increased in the CLL B-lymphocytes when compared to their normal counterparts was nicotinamide-adenine dinucleotide. The level in CLL lymphocytes was 404 versus 209 pmol/10(7) cells for normal B-lymphocytes. No correlation was found between any ribonucleotide levels and the expression of 5'-nucleotidase activity.

B-Lymphocytes↗
PubMed1990

Phosphatidylcholine biosynthesis in castor bean endosperm : purification and properties of cytidine 5'-triphosphate:choline-phosphate cytidylyltransferase.

Cytidine 5'-triphosphate:choline-phosphate cytidylyltransferase (EC 2.7.7.15) has been purified to near homogeneity (3350-fold) from castor bean (Ricinus communis L. var Hale) endosperm. The steps of purification included a differential solubilization of this enzyme with n-octyl beta-d-glucopyranoside (OGP) and column chromatography on sequential DEAE-sepharose, sepharose-6B, and second DEAE-sepharose columns. The uses of appropriate concentrations of the detergent, OGP, in each step were crucial to obtain the highly purified enzyme. The purified enzyme gave a single protein band on nondenaturing polyacrylamide gel electrophoresis. Sodium dodecyl sulfate polyacrylamide gel electrophoresis showed one major protein band of 40 kilodaltons. Gel filtration chromatography indicated that native cytidylyltransferase was approximately 155 kilodaltons, suggesting that it exists naturally as a tetramer. The purified enzyme used methylethanolamine-phosphate as a substrate but not ethanolamine-phosphate and dimethylethanolamine-phosphate. ATP and other nucleotides tested showed little effect on the purified enzyme. The purified enzyme activity was stimulated by both phospholipids extracted from castor bean endosperm and phosphatidylcholineoleate vesicles.

Journal Article↗
PubMed2001

Collaboration between CC- and A-adding enzymes to build and repair the 3'-terminal CCA of tRNA in Aquifex aeolicus.

The universal 3'-terminal CCA sequence of all transfer RNAs (tRNAs) is repaired, and sometimes constructed de novo, by the CCA-adding enzyme [ATP(CTP):tRNA nucleotidyltransferase]. This RNA polymerase has no nucleic acid template, yet faithfully builds the CCA sequence one nucleotide at a time using cytidine triphosphate (CTP) and adenosine triphosphate (ATP) as substrates. All previously characterized CCA-adding enzymes from all three kingdoms are single polypeptides with CCA-adding activity. Here, we demonstrate through biochemical and genetic approaches that CCA addition in Aquifex aeolicus requires collaboration between two related polypeptides, one that adds CC and another that adds A.

Adenosine Triphosphate↗
PubMed1984

Activation of phosphoenolpyruvate-dependent protein kinase by cytidine 5'-triphosphate in rat skeletal muscle.

The effects of nucleotides on phosphoenolpyruvate-dependent protein kinase in rat skeletal muscle were examined. Various ribonucleotide triphosphates were tested and the protein kinase reaction was maximally activated by cytidine 5'-triphosphate followed by uridine 5'-triphosphate and guanosine 5'-triphosphate. No activation by adenosine 5'-triphosphate was observed. Cytidine 5'-diphosphate also activated the reaction but to a significantly lesser extent. Cytidine 5'-monophosphate and cyclic cytidine 3',5'-monophosphate showed no effect whereas cytidine was slightly inhibitory.

Adenosine Triphosphate↗
PubMed1978

Improved radioisotopic assay for cytidine 5'-triphosphate synthetase (EC 6.3.4.2).

An improved radioassay for cytidine 5-triphosphate synthetase is reported which employs thin-layer chromatographic methods and provides a number of advantages over previously available techniques. (i) The method resolves the nucleotides and the degradation products generated during the time course of the enzymatic reaction by ascending chromatography employing polyethyleneimine cellulose plastic-backed sheets. (ii) Determinations of CTP formed and all nucleotide pairs generated during kinetic analysis of CTP synthetase are greatly simplified, further facilitating the detection of extraneous enzymatic activities. (iii) The sensitivity of the assay is enhanced and as little as 50 pmol of product formed was readily detected in supernatant fluids. This was made possible, in part, by the addition of NaF and phosphoenolpyruvate which together maintain the nucleotide triphosphates in the reaction mixture. (iv) A large number of samples can be handled at one time with highly reproducible results. The synthesis of CTP from UTP by enzyme preparations from rat liver, hepatomas, and Salmonella typhimurium LT2 was quantitated with this method.

Animals↗
PubMed1984

Origin of increased deoxycytidine excretion into urine of rats bearing Yoshida ascites sarcoma.

The metabolism of deoxycytidine (dCyd) and dCyd nucleotides in Yoshida ascites sarcoma (YS) cells and the host rat liver was investigated with reference to the increased excretion of urinary dCyd. Incorporation of [14C]orotic acid into the livers of rats at the fifth day after the transplantation of YS cells, the time when the amount of excretion of dCyd in urine was near maximal, was 2 times higher than that into the normal rat livers. After the injection of [14C]orotic acid, the ratio of the specific radioactivity of cytidylate to uridylate moieties of the host liver RNA was measured and found to be higher than that of normal rat liver RNA and to be similar to that of YS cell RNA. When [14C]orotic acid was injected into rats followed by the transplantation of YS cells, the radioactivities present in the livers disappeared more rapidly than those in the control rat livers. The activities of pyrimidine de novo synthesis enzymes, such as cytidine triphosphate synthetase (EC 6.3.4.2) and cytidine diphosphate reductase (EC 1.17.4.1), in YS were higher than those in both rat ascites hepatoma AH 7974 and Walker 256 carcinosarcoma, the transplantations of which did not induce increased excretion of dCyd into urine of the hosts. The activities of dCyd kinase (EC 2.7.1.10) and dCyd deaminase (EC 3.5.4.5) in YS cells were lower than those in the other two tumors investigated. The activities of cytidine triphosphate synthetase and cytidine diphosphate reductase in the livers of YS-bearing rats were elevated compared with those in the livers of rat ascites hepatoma AH 7974- or Walker 256 carcinosarcoma-bearing rats and normal rats, while the activities of dCyd kinase, 5'-nucleotidase (EC 3.1.3.5), and dCyd deaminase were similar between normal rat livers and tumor-bearing rat livers. These results suggest that the increased excretion of urinary dCyd in YS-bearing rats could be caused by both the stimulation of the synthesis of dCyd nucleotides and the low activity of dCyd deaminase in YS cells as well as in the host liver.

Animals↗
PubMed2005

Interaction centres of pyrimidine nucleotides: cytidine-5'-diphosphate (CDP) and cytidine-5'-triphosphate (CTP) in their reactions with tetramines and Cu(II) ions.

The interactions between pyrimidine nucleotides: cytidine-5'-diphosphate (CDP) and cytidine-5'-triphosphate (CTP) and Cu(II) ions, spermine (Spm) and 1,11-diamino-4,8-diazaundecane (3,3,3-tet) have been studied. The composition and stability constants of the complexes formed have been determined by means of the potentiometric method, while the centres of interactions in the ligands have been identified by the spectral methods (UV-Vis, Ultraviolet and Visible spectroscopy; EPR, electron spin resonance; NMR). In the systems without metal, formation of the molecular complexes nucleotide-polyamine with the interaction centres at the endocyclic nitrogen atom of purine ring N3, the oxygen atoms of the phosphate group from the nucleotide and protonated nitrogen atoms of the polyamine have been detected. Significant differences have been found in the metallation between the systems with Spm and with 3,3,3-tet. In the systems with spermine, mainly protonated species are formed with the phosphate group of the nucleotide and deprotonated nitrogen atoms of the polyamine making the coordination centres, while the donor nitrogen atom of the nucleotide N3 is involved in the intramolecular interligand interactions, additionally stabilising the complex. In the systems with 3,3,3-tet, the MLL' type species are formed in which the oxygen atoms of the phosphate group and nitrogen atoms of the polyamine are involved in metallation, whereas the N3 atom from the pyrimidine ring of the nucleotide is located outside the inner coordination sphere of copper ion. The main centre of Cu(II) interaction in the nucleotide, both in the system with Spm and 3,3,3-tet is the phosphate group of the nucleotide.

Amines↗
PubMed1997

Cloning and sequencing of the pyrG encoding cytidine 5'-triphosphate synthetase from Mycobacterium bovis BCG.

The pyrG gene encoding cytidine 5'-triphosphate (CTP) synthetase which catalyzes the terminal reaction for de novo synthesis of pyrimidine nucleotides was cloned and sequenced from Mycobacterium bovis BCG. The BCG pyrG was screened in lambda ZAPII library employing a DNA probe which was constructed from PCR based on a consensus pattern of glutamine amidotransferase type I. The BCG CTP synthetase deduced from a nucleotide sequence consisting of 586 amino acid residues with a calculated molecular weight of 63,642 daltons. Alignment of BCG CTP synthetase with all sequences available in GenBank indicates that the residues suggested as a catalytic triad for glutamine hydrolysis at the carboxyl terminal domain and an amino terminal segment are completely conserved among all CTP synthetases.

Amino Acid Sequence↗
PubMed2003

Limited proteolysis of Escherichia coli cytidine 5'-triphosphate synthase. Identification of residues required for CTP formation and GTP-dependent activation of glutamine hydrolysis.

Cytidine 5'-triphosphate synthase catalyses the ATP-dependent formation of CTP from UTP using either ammonia or l-glutamine as the source of nitrogen. When glutamine is the substrate, GTP is required as an allosteric effector to promote catalysis. Limited trypsin-catalysed proteolysis, Edman degradation, and site-directed mutagenesis were used to identify peptide bonds C-terminal to three basic residues (Lys187, Arg429, and Lys432) of Escherichia coli CTP synthase that were highly susceptible to proteolysis. Lys187 is located at the CTP/UTP-binding site within the synthase domain, and cleavage at this site destroyed all synthase activity. Nucleotides protected the enzyme against proteolysis at Lys187 (CTP > ATP > UTP > GTP). The K187A mutant was resistant to proteolysis at this site, could not catalyse CTP formation, and exhibited low glutaminase activity that was enhanced slightly by GTP. K187A was able to form tetramers in the presence of UTP and ATP. Arg429 and Lys432 appear to reside in an exposed loop in the glutamine amide transfer (GAT) domain. Trypsin-catalyzed proteolysis occurred at Arg429 and Lys432 with a ratio of 2.6 : 1, and nucleotides did not protect these sites from cleavage. The R429A and R429A/K432A mutants exhibited reduced rates of trypsin-catalyzed proteolysis in the GAT domain and wild-type ability to catalyse NH3-dependent CTP formation. For these mutants, the values of kcat/Km and kcat for glutamine-dependent CTP formation were reduced approximately 20-fold and approximately 10-fold, respectively, relative to wild-type enzyme; however, the value of Km for glutamine was not significantly altered. Activation of the glutaminase activity of R429A by GTP was reduced 6-fold at saturating concentrations of GTP and the GTP binding affinity was reduced 10-fold. This suggests that Arg429 plays a role in both GTP-dependent activation and GTP binding.

Amino Acid Sequence↗
PubMed1982

Aggregation of rat neutrophils by nucleotide triphosphates.

1 Adenosine 5'-triphosphate (ATP) and uridine 5'-triphosphate (UTP) at concentrations of 3 x 10(-7)M and greater cause a rapid partially reversible aggregation of rat polymorphonuclear leucocytes. 2 Other nucleotide phosphates are much less active at producing aggregation responses; the agonist potencies being UTP greater than ATP greater than guanosine 5'-triphosphate, cytidine 5'-triphosphate, thymidine 5'-triphosphate; ATP greater than adenosine 5'-diphosphate (ADP) greater than adenosine 5'-monophosphate (AMP); and ADP greater than uridine 5'-diphosphate, thymidine 5'-diphosphate, guanosine 5'-diphosphate, cytidine 5'-diphosphate. Adenosine is inactive. 3 The hydrolysis resistant analogues of ATP, alpha-beta-methylene ATP and beta-gamma-methylene ATP, do not cause neutrophil aggregation suggesting that hydrolysis of ATP and UTP may be required to initiate the aggregation response. 4 It is postulated that ATP and UTP may be important stimulants of neutrophil function and may be involved in the adherence of these cells to the vascular endothelium.

Adenosine Diphosphate↗
PubMed1997

Calcium-mobilizing purine receptors on the surface of mammalian articular chondrocytes.

If we are to fully understand mechanisms of cartilage homeostasis, it is essential that we know the full catalogue of receptors present on the surface of a chondrocyte and the pathways regulated by ligands that bind to these receptors. In this study, we describe chondrocyte responses to adenosine 5'-triphosphate and related molecules. Adenosine 5'-triphosphate stimulated a statistically significant, dose-dependent, transient rise in the concentration of calcium ions in Fura 2-loaded, differentiated, primary chondrocytes. The increase occurred in the absence of extracellular calcium, indicating a mobilization from intracellular stores. The increase in concentration of cytoplasmic calcium ions induced by adenosine 5'-triphosphate was mimicked by uridine 5'-triphosphate but not by 2-methylthioadenosine 5'-triphosphate, cytidine 5'-triphosphate, or adenosine. Heterologous desensitization experiments demonstrated that chondrocytes showed no subsequent response to uridine 5'-triphosphate after initial stimulation with adenosine 5'-triphosphate nor did they respond to adenosine 5'-triphosphate in inverse conditions, thereby indicating competition for the same receptor site. Together, these results are consistent with the presence of a P2U receptor on the cell surface of chondrocytes. Purine-induced calcium mobilization in passaged chondrocytes showed the same pharmacological profile with respect to agonist sensitivity, but responses were of greater magnitude than responses in primary differentiated chondrocytes, suggesting upregulation of the receptor with time in culture. Adenosine 5'-triphosphate and uridine 5'-triphosphate (1-100 microM) did not alter cartilage matrix synthesis as measured by rate of incorporation of [35S]sulfate into glycosaminoglycan by cartilage explants or primary chondrocytes. Matrix degradation, measured by release of glycosaminoglycan from cartilage explants, was also unaltered by adenosine 5'-triphosphate or uridine 5'-triphosphate (1-100 microM). Production of prostaglandin E2 was upregulated by incubation with either adenosine 5'-triphosphate or uridine 5'-triphosphate. These data demonstrate the presence of a functional P2U-like purine receptor on the surface of primary articular chondrocytes and support the hypothesis that altered concentrations of extracellular purines may influence chondrocyte metabolism.

Adenosine Triphosphate↗
PubMed1985

A firefly luciferase assay for determination of cytidine 5'-triphosphate in biological samples.

A routine assay for CTP in cell and tissue extracts using crude firefly lantern preparations is described. ATP, GTP, and UTP are removed by incubation of the samples with a mixture of 3-phosphoglycerate kinase, hexokinase, glucose-6-phosphate dehydrogenase, and UDP-glucose pyrophosphorylase in the presence of ADP. The method is sensitive (greater than 30 nM CTP), inexpensive, and reproducible. No chromatographic purification of the biological samples or of the firefly extract is necessary. Corrections must be made for some loss of CTP during the enzymatic incubation and for the background luminescence of ADP. The applicability of the assay is tested with extracts from the cyanobacterium Anacystis nidulans.

Adenosine Diphosphate↗
PubMed1975

Photoactivation of NAD Kinase through Phytochrome: Phosphate Donors and Cofactors.

The specificities of phosphate donors and the effects of metal chelating agents and divalent metal ions on NAD kinase activation by phytochrome-far red-absorbing form (Pfr) were examined. ATP was the most efficient phosphorylating agent. Uridine 5'-triphosphate, cytidine 5'-triphosphate (CTP), inosine 5'-triphosphate, and guanosine 5'-triphosphate in this order caused significant phosphorylation in the dark. Under red light, striking photoactivation of NAD kinase was obtained with ATP and subsequently CTP.In the presence of exogenous Mg(2+), which is required for NAD kinase activity, alpha-nitroso-beta-naphthol, cyanide, and dimethylglyoxime, strongly inhibited the activation by red light without affecting the level of NAD kinase in the dark.Of the divalent cations tested with the KCN-treated phytochrome preparation, only Co(2+) was effective for photoactivation of NAD kinase. Even when Mg(2+), an essential component of NAD kinase, was added to the assay system, the further addition of Co(2+) was required for the activation of NAD kinase by Pfr.

Journal Article↗
PubMed1992

The nucleotide receptors on mouse C2C12 myotubes.

1. The response of C2C12 mouse myotubes to stimulation with adenosine triphosphate (ATP) and other nucleotides was studied by measuring changes in membrane potential. 2. A transient hyperpolarization followed by a slowly declining depolarization of the cells was observed in the presence of ATP (10 microM-1 mM). 3. The hyperpolarization was not observed in the absence of external calcium, and was abolished in the presence of tetraethylammonium (20 mM) or the bee toxin, apamin (0.1 microM). The depolarization was reduced under low sodium conditions. 4. A biphasic change in membrane potential was also recorded in the presence of adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S) and the pyrimidine uridine triphosphate (UTP), while the ATP derivatives and analogues, adenosine diphosphate, adenosine, alpha,beta-methylene ATP and 2-methylthio ATP and the nucleotides, guanosine triphosphate and cytidine triphosphate, did not affect the membrane potential of the myotubes. 5. The hyperpolarization elicited by ATP gamma S or UTP was also blocked by apamin and abolished under Ca(2+)-free conditions. 6. In contrast to ATP and ATP gamma S, the depolarization evoked by UTP was unaffected under low Na+ and less sensitive to the antagonistic action of suramin. 7. The ATP and UTP responses at maximal concentration were not additive after simultaneous application. ATP elicited a depolarization if applied after UTP, while UTP did not change membrane potential following the application of ATP. 8. The concentration-response curves of the effective nucleotides were shifted to the right in the presence of suramin, suggesting competitive antagonism.9. These results can be explained by the presence of 'nucleotide receptors' mediating the ATP/UTPinduced hyperpolarization and depolarization in C2C12 myotubes. Furthermore, an increase in Na+-conductivity can be exclusively activated by ATP.

Adenosine Triphosphate↗