Document Detail


Structure-affinity relationship in the interactions of human organic anion transporter 1 with caffeine, theophylline, theobromine and their metabolites.
MedLine Citation:
PMID:  16038872     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
It is well known that human organic anion transporter 1 (hOAT1) transports many kinds of drugs, endogenous compounds, and toxins. However, little is known about the structure-affinity relationship. The aim of this study was to elucidate the structure-affinity relationship using a series of structurally related compounds that interact with hOAT1. Inhibitory effects of xanthine- and uric acid-related compounds on the transport of p-aminohippuric acid were examined using CHO-K1 cells stably expressing hOAT1. The order of potency for the inhibitory effects of xanthine-related compounds on PAH uptake was 1-methyl derivative>7-methyl derivative>3-methyl derivative falling dotsxanthine>1,3,7-trimethyl derivative (caffeine). The order of potency of the inhibition was 1,3,7-trimethyluric acid>1,3-dimethyluric acid>1,7-dimethyluric acid>1-methyluric acid>uric acid. A significant correlation between inhibitory potency and lipophilicity of the tested uric acid-related compounds was observed. The main determinant of the affinity of xanthine-related compounds is the position of the methyl group. On the other hand, lipophilicity is the main determinant of the affinity of uric acid-related compounds.
Authors:
Mitsuru Sugawara; Takahiro Mochizuki; Yoh Takekuma; Katsumi Miyazaki
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1714     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2005 Aug 
Date Detail:
Created Date:  2005-08-16     Completed Date:  2005-09-22     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  85-92     Citation Subset:  IM    
Affiliation:
Department of Pharmacy, Hokkaido University Hospital, Kita-14-jo, Nishi-5-chome, Kita-ku, Sapporo, Hokkaido 060-8648, Japan. msuga@med.hokudai.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Animals
Biological Transport
CHO Cells
Caffeine / chemistry,  pharmacology
Cricetinae
Cricetulus
Humans
Molecular Structure
Organic Anion Transport Protein 1 / antagonists & inhibitors*,  metabolism
Theobromine / chemistry,  pharmacology
Theophylline / chemistry,  pharmacology
Uric Acid / chemistry,  pharmacology
Xanthines / chemistry*,  pharmacology*
p-Aminohippuric Acid / metabolism
Chemical
Reg. No./Substance:
0/Organic Anion Transport Protein 1; 0/Xanthines; 58-08-2/Caffeine; 58-55-9/Theophylline; 61-78-9/p-Aminohippuric Acid; 69-93-2/Uric Acid; 83-67-0/Theobromine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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