| 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 |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| 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
Previous Document: Modulation of photosynthetic electron transport in the absence of terminal electron acceptors: chara...
Next Document: Externalizing and personalizing biases in persecutory delusions: the relationship with poor insight ...