| Effect of 5-benzylacyclouridine, a potent inhibitor of uridine phosphorylase, on the metabolism of circulating uridine by the isolated rat liver. | |
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MedLine Citation:
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PMID: 6870929 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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5-Benzylacyclouridine (BAU) is a specific inhibitor of uridine phosphorylase, the first enzyme in the catabolism of uridine. It was found that 20 and 100 microM BAU dramatically reduced the rapid clearance of trace amounts of either [14C]uridine or hyperphysiologic concentrations of non-labeled uridine by the isolated rat liver perfused with an artificial oxygen carrier. In the absence of exogenously added uridine, non-treated livers maintained circulating concentrations of 1-2 microM uridine. In the presence of 20 microM BAU, these concentrations were increased 2- to 3-fold higher than physiologic levels (1.4 +/- 0.6 microM) and remained elevated for the duration of the experiment (120-160 min). In the presence of 100 microM BAU, uridine concentrations rose continuously at rates of between 80 and 150 nmoles per hr per g of liver, and the clearance of a single radioactive spike of uridine was reduced extensively. The half-life of a uridine spike was extended 2-fold in the presence of 20 microM BAU and 5- to 6-fold in the presence of 100 microM BAU. Exogenously added uridine (15 and 40 microM) was cleared rapidly by nontreated livers, with a half-life of approximately 10 min. However, BAU at a concentration of 20 microM increased the half-life of 15 or 40 microM uridine added to the perfusate by approximately 10-fold. A 100 microM concentration of BAU inhibited the removal of 40 microM circulating uridine, but with 15 microM uridine there was a continuous increase in the circulating concentration similar to that seen in the absence of added uridine. We conclude that extensive inhibition of uridine phosphorylase occurs at 100 microM BAU and partial inhibition at 20 microM BAU. These data indicate independent catabolic and excretory functions of the rat liver with respect to uridine. |
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Authors:
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A Monks; O Ayers; R L Cysyk |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Biochemical pharmacology Volume: 32 ISSN: 0006-2952 ISO Abbreviation: Biochem. Pharmacol. Publication Date: 1983 Jul |
Date Detail:
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Created Date: 1983-08-26 Completed Date: 1983-08-26 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0101032 Medline TA: Biochem Pharmacol Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 2003-9 Citation Subset: IM |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Kinetics Liver / drug effects, metabolism* Pentosyltransferases / antagonists & inhibitors* Perfusion Rats Rats, Inbred Strains Uracil / analogs & derivatives*, pharmacology Uridine / blood, metabolism* Uridine Phosphorylase / antagonists & inhibitors* |
| Chemical | |
Reg. No./Substance:
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58-96-8/Uridine; 66-22-8/Uracil; 82857-69-0/5-benzylacyclouridine; EC 2.4.2.-/Pentosyltransferases; EC 2.4.2.3/Uridine Phosphorylase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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