Document Detail

Adenosine A(1) receptors do not play a major role in the regulation of lipogenic gene expression in hepatocytes.
MedLine Citation:
PMID:  22449383     Owner:  NLM     Status:  Publisher    
Activation of adenosine A(1) receptors was reported to promote fatty acid synthesis in AML-12 cells, by increasing the expression of SREBP-(1c) (sterol regulatory binding protein 1c) and FAS (fatty acid synthase). Since these findings have important therapeutic implications for the discovery of adenosine A(1) receptor agonists, further studies were undertaken to determine the expression and functional relevance of adenosine A(1) receptor in the liver. To that end, we used two classes of distinct adenosine A(1) receptor agonists: CPA (N(6)-cyclopentyl-adenosine), a full agonist and GS-9667 (2-{6-[((1R,2R)-2-hydroxycyclopentyl)-amino]purin-9-yl}(4S,5S,2R,3R)-5-[(2-fluorophenylthio)methyl]-oxolane-3,4-diol), a partial agonist. Treatment of AML-12 cells, HepG2 cells and primary human hepatocytes with either CPA or GS-9667 did not increase the gene expression of SREBP-(1c) or FAS. Furthermore, in AML-12 and HepG2 cells, CPA did not antagonize forskolin-stimulated cAMP production, a characteristic of adenosine A(1) receptor activation, indicating that these cells lack adenosine A(1) receptor function. Consistent with this finding, adenosine A(1) receptor gene expression was found to be very low and adenosine A(1) receptor protein levels were hardly detectable by radioligand binding assays in hepatic cell lines such as AML-12 and HepG2 as well as in both mouse and human liver tissues. Finally, acute treatment with adenosine A(1) receptor agonist GS-9667 had no significant effect on gene expression of both SREBP-(1c) and FAS in livers of Sprague Dawley rats. Taken together, our data suggest that the expression of adenosine A(1) receptor is too low to play a major role in the regulation of lipogenic genes in hepatocytes.
Ming Yang; Ruth Chu; Jeffrey W Chisholm; Holger Doege; Luiz Belardinelli; Arvinder K Dhalla
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-16
Journal Detail:
Title:  European journal of pharmacology     Volume:  -     ISSN:  1879-0712     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-3-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier B.V.
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