Document Detail

Regional heterogeneities in the production of uric acid from adenosine in the bivascularly perfused rat liver.
MedLine Citation:
PMID:  10395085     Owner:  NLM     Status:  MEDLINE    
The heterogeneity of the liver parenchyma in relation to uric acid production from adenosine was investigated using the bivascularly perfused rat liver in the anterograde and retrograde modes. Adenosine was infused in livers from fed rats during 20 min at four different concentrations (20, 50, 100 and 200 microM) according to four experimental protocols as follows: (A) anterograde perfusion, with adenosine infusion into the portal vein; (B) anterograde perfusion, with adenosine in the hepatic artery, (C) retrograde perfusion, with adenosine in the hepatic vein; (D) retrograde perfusion, with adenosine in the hepatic artery. With protocols A, B, and D uric acid production from adenosine was always characterized by initial bursts followed by progressive decreases toward smaller steady-states. With protocol C the initial burst was present only when 200 microM adenosine was infused. The initial bursts in uric acid production were accompanied by simultaneous increases in the ratio of uric acid production/adenosine uptake rate. These initial bursts are thus representing increments in the production of uric acid that are not corresponded by similar increments in the metabolic uptake rates of adenosine. Global analysis of uric acid production revealed that the final steady-state rates were approximately equal for all infusion rates with protocols A, B and C, but smaller with protocol D. This difference, however, can be explained in terms of the differences in accessible cellular spaces, which are much smaller when protocol D is employed. When the analysis was performed in terms of the extra amounts of uric acid produced during the infusion of adenosine, where the initial bursts are also taken into account, different dose-response curves were found for each experimental protocol. These differences cannot be explained in terms of the accessible cell spaces and they are likely to reflect regional heterogeneities. From the various dose-response curves and from the known characteristics of the microcirculation of the rat liver it can be concluded that the initial bursts in uric acid production are generated in periportal hepatocytes. The reason for this heterogeneity could be related to the metabolic effects of adenosine, especially to oxygen uptake inhibition, which is likely to produce changes in the ATP/AMP ratios.
T R Fernandes; F Suzuki-Kemmelmeier; E L Ishii-Iwamoto; J Constantin; A Bracht
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular and cellular biochemistry     Volume:  195     ISSN:  0300-8177     ISO Abbreviation:  Mol. Cell. Biochem.     Publication Date:  1999 May 
Date Detail:
Created Date:  1999-10-28     Completed Date:  1999-10-28     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0364456     Medline TA:  Mol Cell Biochem     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  207-17     Citation Subset:  IM    
Laboratory of Liver Metabolism, University of Maringá, Brazil.
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MeSH Terms
Adenosine / administration & dosage,  metabolism*
Hepatic Artery / metabolism
Hepatic Veins / metabolism
Infusions, Intravenous
Liver / blood supply,  chemistry,  metabolism*
Oxygen Consumption
Perfusion* / methods
Portal Vein / metabolism
Rats, Wistar
Uric Acid / metabolism*
Reg. No./Substance:
58-61-7/Adenosine; 69-93-2/Uric Acid

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