Drugs online research references
mds.qmw.ac.uk
Xanthine oxidoreductase (XOR) is a mammalian enzyme that possesses a series of redox centers, which use either NAD(+) or molecular oxygen for oxidation of the purines xanthine and hypoxanthine to uric acid. The ability of XOR to act as an NADH oxidase is a less well recognized function of the enzyme, and it is this function that we used to explore the metabolism of glyceryl trinitrate. The antiplatelet effect of nitric oxide (NO) on platelet aggregation was used as a bioassay to assess the bioconversion of glyceryl trinitrate to NO by XOR. The thromboxane mimetic U46619, 2 microM, was used to stimulate platelet aggregation in platelet-rich plasma prepared from healthy drug-free human volunteers. All incubations were carried out at 37 degrees C for 2 min after the addition of U46619. XOR produced a dose-dependent antiaggregant effect when incubated with glyceryl trinitrate (GTN), 220 microM. This did not occur when GTN or XOR was incubated with platelet-rich plasma independently. The antiaggregant effect of XOR plus GTN was dose dependently inhibited by allopurinol, with an IC(50) of 100 microM. The addition of superoxide dismutase (SOD), 100 U/ml produced a shift to the left in the antiaggregant dose-response curve for XOR. The IC(50) for XOR at 200 U/l without SOD was decreased to 80 U/l with SOD. Oxyhemoglobin, an extracellular NO scavenger, produced a dose-dependent, noncompetitive inhibition of the antiaggregant effect of XOR plus GTN. These findings suggest that GTN may be reduced to NO in vitro by the enzyme XOR in sufficient amounts to inhibit platelet aggregation.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10604966&dopt=Abstract
Cancer Res. 1983 Sep;43(9):4098-101.
Absence of hypoxanthine:guanine phosphoribosyltransferase activity in murine Dunn osteosarcoma.
Abelson HT, Gorka C.
The transplantable murine Dunn osteosarcoma has no detectable hypoxanthine:guanine phosphoribosyltransferase (EC 2.4.2.8) activity. This was established from the tumors directly and from tissue culture cell lines derived from the tumor using a variety of assays: e.g., no [3H]hypoxanthine uptake into tumor or tissue culture cells, no conversion of [3H]hypoxanthine to [3H]IMP by cell extracts from tumors or tissue culture cells, no growth of tissue culture cells in hypoxanthine:aminopterin:thymidine medium, and normal growth of these cells in 10 microM 6-mercaptopurine. Ten human osteosarcomas have been assayed, and two have no apparent hypoxanthine:guanine phosphoribosyltransferase enzyme activity. After high-dose methotrexate treatment in vivo, murine tumors could be selectively killed and normal tissues could be spared by using a rescue regimen of hypoxanthine-thymidine-allopurinol.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6575863&dopt=Abstract
J Neurochem. 1985 Feb;44(2):574-9.
Identification of hypoxanthine transport and xanthine oxidase activity in brain capillaries.
Betz AL.
Microvessel segments were isolated from rat brain and used for studies of hypoxanthine transport and metabolism. Compared to an homogenate of cerebral cortex, the isolated microvessels were 3.7-fold enriched in xanthine oxidase. Incubation of the isolated microvessels with labeled hypoxanthine resulted in its rapid uptake followed by the slower accumulation of hypoxanthine metabolites including xanthine and uric acid. The intracellular accumulation of these metabolites was inhibited by the xanthine oxidase inhibitor allopurinol. Hypoxanthine transport into isolated capillaries was inhibited by adenine but not by representative pyrimidines or nucleosides. Similar results were obtained when blood to brain transport of hypoxanthine in vivo was measured using the intracarotid bolus injection technique. Thus, hypoxanthine is transported into brain capillaries by a transport system shared with adenine. Once inside the cell, hypoxanthine can be metabolized to xanthine and uric acid by xanthine oxidase. Since this reaction leads to the release of oxygen radicals, it is suggested that brain capillaries may be susceptible to free radical mediated damage. This would be most likely to occur in conditions where the brain hypoxanthine concentration is increased as following ischemia.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3838099&dopt=Abstract
online pharmacies ||
Hair Million herbal formula for hair loss and hair growth ||
Amoxicillin ||
Tramadol ||
Paxil ||
Rx Drugs USA, Prescription Drugs Online Pharmacy ||
Zithromax ||
online pharmacy ||
Antibiotics and prescription medications online literature ||
Antibiotics