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At least 289 records · Page 16Linked to original sources
PubMed1993

Simultaneous determination of nerve-induced adenine nucleotides and nucleosides released from rabbit pulmonary artery.

Electrical field stimulation elicits the release of catecholamines, adenine nucleotides, and adenosine from the rabbit pulmonary artery in a frequency dependent manner. To enhance our ability to investigate the release of endogenous adenine nucleotides and adenosine from this and other biological preparations, a new analytical procedure has been developed. This procedure involves the use of an internal standard, 9-beta-D-arabinofuranosyladenine (IS), the derivatization of ATP, ADP, AMP, adenosine (Ado), and IS with chloroacetaldehyde, the isocratic high-performance liquid chromatographic separation of these ethenopurine derivatives on an Ultron N-phenyl HPLC column, and their detection and quantitation by fluorescence spectroscopy. This procedure has enhanced sensitivity and reliability over existing procedures due to the stability of the chromatographic baseline and the use of an internal standard. When this analytical procedure was utilized to measure the adenine nucleotides and Ado that are released from the rabbit pulmonary artery in response to electrical field stimulation, it was observed that the release of endogenous ATP, ADP, AMP, and Ado exceeded that of endogenous norepinephrine. A molar ratio (6-amino purines:catecholamines) of approximately 2000:1 was obtained at a stimulation frequency of 16 Hz. This observation suggests an important extracellular role for adenine nucleotides and nucleosides in the physiology of vascular tissues.

Acetaldehyde↗
PubMed2006

Nucleoside and nucleotide inhibitors of HIV-1 replication.

HIV-1 reverse transcriptase (RT) is one of the main targets for antiviral therapy. Two classes of RT inhibitors can be distinguished: those that are nucleoside or nucleotide analogues (sharing the common NRTIs abbreviation) and those that are not. This review focuses on the NRTIs, which are highly efficient in slowing down viral replication and are used in combination regimens. Unfortunately, the current inhibitors do not completely suppress viral replication and due to the high capacity of adaptation of HIV, allow the selection of drug-resistant viruses. Resistance mechanisms to NRTIs have been extensively investigated and can be divided into two types: improved discrimination of a nucleotide analogue relative to the natural substrate or increased phosphorolytic cleavage of an analogue-blocked primer. This knowledge is important both for the development of new drugs designed to target resistant strains and for the development of new antiviral strategies. The NRTIs currently in clinical trials and new developments in this area are also reviewed.

Drug Resistance, Viral↗
PubMed1990

Nerve and drug-induced release of adenine nucleosides and nucleotides from rabbit aorta.

The purpose of the present study was to assess the possible sites which contribute to the nerve stimulation- and alpha-agonist-induced overflow of endogenous adenine nucleosides and nucleotides in vascular tissue. Particular attention was focused on the endothelium because it is known that endothelial cells have a high concentration of ATP and its metabolites. Segments of rabbit thoracic aorta, some denuded of endothelial cells by rubbing the lumen of the vessel, were incubated in organ baths and subjected to transmural nerve stimulation or stimulated with the alpha-1 adrenoceptor agonist methoxamine. A portion of the bathing solution was processed for the determination of norepinephrine by high-performance liquid chromatography with electrochemical detection and a portion for determination of ATP, ADP, AMP and adenosine by high-performance liquid chromatography with fluorescence detection. Transmural stimulation led to a significant release of both norepinephrine and the adenine nucleosides and nucleotides in a ratio of 1 to 350. Removal of the endothelium did not change the release of norepinephrine but reduced the release of adenosine and its derivatives by 90%. Methoxamine also caused the release of adenosine and the adenine nucleotides which was reduced by 93% by removal of the endothelium. Thus, the endothelium seems to be a major source of transmural nerve stimulation and alpha-agonist induced overflow of adenosine and adenine nucleotides. The endothelium is not the exclusive source of these purine congeners, however. In the case of transmural stimulation there is approximately 10% of the total which is independent of the endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗
PubMed2003

Ring-expanded ("fat") nucleoside and nucleotide analogues exhibit potent in vitro activity against flaviviridae NTPases/helicases, including those of the West Nile virus, hepatitis C virus, and Japanese encephalitis virus.

A series of ring-expanded ("fat") heterocycles, nucleoside and nucleotide analogues (RENs) containing the imidazo[4,5-e][1,3]diazepine ring system (9, 14, 15, 18, 24-26, 28, 31, and 33) and imidazo[4,5-e][1,2,4]triazepine ring systems (30b, 30c, 32, and 34), have been synthesized as potential inhibitors of NTPases/helicases of Flaviviridae, including the West Nile virus (WNV), hepatitis C virus (HCV), and Japanese encephalitis virus (JEV). An amino-terminal truncated form of human enzyme Suv3(delta1-159) was also included in the study so as to assess the selectivity of RENs against the viral enzymes. The analogues of RENs included structural variations at position 1 of the heterocyclic base and contained changes in both the type of sugar moieties (ribo, 2'-deoxyribo, and acyclic sugars) and the mode of attachment (alpha versus beta anomeric configuration) of those sugars to the heterocyclic base. The target RENs were biochemically screened separately against the helicase and ATPase activities of the viral NTPases/helicases. A number of RENs inhibited the viral helicase activity with IC50 values that ranged in micromolar concentrations and exhibited differential selectivity between the viral enzymes. In view of the observed tight complex between some nucleosides and RNA and/or DNA substrates of a helicase, the mechanism of action of RENs might involve their interaction with the appropriate substrate through binding to the major or minor groove of the double helix. The REN-5'-triphosphates, on the other hand, did not influence the above unwinding reaction, but instead exerted the inhibitory effect on the ATPase activity of the enzymes. The activity was found to be highly dependent upon the low concentration levels of the substrate ATP. At concentrations >500 microM of RENs and the ATP concentrations >10 times the Km value of the enzyme, a significant activation of NTPase activity was observed. This activating effect underwent further dramatic enhancement (>1000%) by further increases in ATP concentration in the reaction mixture. A tentative mechanistic model has been proposed to explain the observed results, which includes an additional allosteric binding site on the viral NTPases/helicases that can be occupied by nucleoside/nucleotide-type molecules such as RENs.

Adenosine Triphosphatases↗
PubMedDate not supplied

Role of nucleosides and nucleotide mixture in intestinal mucosal growth under total parenteral nutrition.

The preventive effect of a mixture of nucleosides and a nucleotide (OG-VI) on total parenteral nutrition (TPN)-associated gut mucosal atrophy was investigated. Male Wistar rats were randomly divided into two groups. The TPN group (n = 11) received a standard TPN diet (250 kcal and 1.78 g nitrogen.kg-1.day-1) for 6 days; the TPN + OG-VI group (n = 10) received OG-VI (2.5 ml.kg-1.day-1) in addition to the standard TPN solution for 6 days. To obtain information on a normal fed condition of the intestine, another 10 rats were maintained on oral rat chow for 6 days. Compared with the TPN group, mucosal wet weights in the jejunum (22.8 +/- 1.8 vs. 20.5 +/- 2.0 mg/cm) and the ileum (19.4 +/- 2.2 vs. 16.8 +/- 2.3 mg/cm) were significantly greater in the TPN + OG-VI group. Likewise, diamine oxidase activities in the jejunum (13.7 +/- 4.27 vs. 8.02 +/- 3.40 nmol.min-1.cm-1) and the ileum (33.9 +/- 6.89 vs. 25.9 +/- 7.93 nmol.min-1.cm-1) were significantly higher in the TPN + OG-VI group. Moreover, the bromodeoxyuridine labeling index in the TPN + OG-VI group (36.9 +/- 4.30%) was significantly higher than in the TPN group (31.0 +/- 3.03%). The addition of OG-VI to the standard TPN diet improved mucosal growth and maturity by increasing the proliferating activity of crypt cells. External provision of purines and pyrimidines may be necessary to sustain mucosal function during TPN.

Amine Oxidase (Copper-Containing)↗
PubMed1992

Quinacrine-staining of neurones, and activity of purine nucleosides and nucleotides in marine and terrestrial invertebrates from several phyla.

1. The acridine derivative quinacrine was used to stain nerve fibres in internal organs of 17 species of marine and terrestrial invertebrates from seven different phyla. 2. The majority of preparations showed quinacrine-stained nerve fibres. There was a degree of variation, ranging from a dense network of nerve bundles to single fibres. Quinacrine-positive nerve cell bodies were also observed in some ganglia. 3. Pharmacological experiments were performed on a variety of isolated tissues from the different marine and terrestrial groups, in order to ascertain their sensitivity to adenine nucleosides and nucleotides. 4. Correlation is drawn between the ability of neurones within a tissue to bind quinacrine, and the ability of that tissue to respond to applied adenine nucleosides and nucleotides.

Animals↗
PubMed1989

The effect of exogenously-supplied nucleosides and nucleotides and the involvement of adenosine 3':5'-cyclic monophosphate (cyclic AMP) in the yeast mycelium transition of Ceratocystis (= Ophiostoma) ulmi.

The yeast-mycelium transition of Ceratocystis (= Ophiostoma) ulmi (NRRL 6404) was induced by exogenously-supplied nucleosides and nucleotides in defined liquid media. During the yeast-mycelium transition, intracellular adenosine 3':5'-cyclic monophosphate (cAMP) levels increased and maximum levels coincided with maximum germination. This, coupled with findings that the cAMP phosphodiesterase inhibitors, theophylline and caffeine, also induced germination and elevated levels of intracellular cAMP, indicated the involvement of cAMP in the regulation of the yeast-mycelium transition.

Ascomycota↗
PubMed2005

Antiadenovirus activities of several classes of nucleoside and nucleotide analogues.

The absence of any formally licensed antiadenovirus drugs and the increasing incidence of life-threatening adenovirus infections in immunosuppressed patients warrant the development of effective antiadenovirus compounds. A detailed study was performed on the antiadenovirus activities of several classes of nucleoside and nucleotide analogues in human embryonic lung fibroblast cells. The antiadenovirus activities were evaluated by three methods, viz., evaluating the adenoviral cytopathic effect, monitoring cell viability by a colorimetric assay, and real-time PCR quantitation of viral DNA as a direct parameter for virus replication. The most active and selective compounds were the acyclic nucleoside phosphonate analogues cidofovir, its adenine analogue (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], and the new derivative (S)-2,4-diamino-6-[3-hydroxy-2-(phosphonomethoxy)propoxy]pyrimidine [(S)-HPMPO-DAPy]; the N7-substituted acyclic derivative 2-amino-7-(1,3-dihydroxy-2-propoxymethyl)purine (S-2242); and the 2',3'-dideoxynucleoside analogues zalcitabine and alovudine. No antiadenovirus activity was observed for the antiviral drugs ribavirin, foscarnet, acyclovir, penciclovir, and brivudin, while ganciclovir displayed modest activity. However, in human osteosarcoma cells transfected with herpes simplex virus thymidine kinase, ganciclovir demonstrated highly potent antiadenovirus activity, suggesting that the efficacy of ganciclovir against adenovirus is limited by inefficient phosphorylation in adenovirus-infected cells, rather than by insufficient inhibition at the viral DNA polymerase level. Collectively, our antiviral data show that the adenovirus DNA polymerase exhibits sensitivity to a relatively broad spectrum of inhibitors and should be studied further as an antiviral target in antiadenovirus drug development programs.

Adenoviridae↗
PubMed1992

Effects of adenine nucleosides and nucleotides on the isolated heart of the snail Helix aspersa and the slug Arion ater.

1. Adenine nucleosides and nucleotides were examined for pharmacological activity in hearts isolated from the snail Helix aspersa and the slug Arion ater. 2. Adenosine, AMP, ADP and ATP (above 100 microM) produced either an excitation or an inhibition in the isolated hearts of the snail and slug. 3. 2-Chloroadenosine, alpha, beta-methylene ATP and 2-methylthio ATP were inactive at concentrations up to 1 mM. 4. Responses were not blocked by any commonly accepted vertebrate purinoceptor antagonists, indicating that these purinoceptors are dissimilar to vertebrate purinoceptors and cannot be classified according to accepted purinoceptor classifications. 5. Electrical field stimulation of the snail heart produced frequency-dependent responses: 1-4 Hz produced predominantly excitation, 8-32 Hz predominantly inhibition. These responses were unaffected by the purines up 3 mM.

Adenine Nucleotides↗