Document Detail


Transport of monocarboxylic acids at the blood-brain barrier: studies with monolayers of primary cultured bovine brain capillary endothelial cells.
MedLine Citation:
PMID:  1890627     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The kinetics and mechanism of the transport of monocarboxylic acids (MCAs) were studied by using primary cultured bovine brain capillary endothelial cells. Concentration-dependent uptake of acetic acid was observed, and the kinetic parameters were estimated as follows: the Michaelis constant, Kt, was 3.41 +/- 1.87 mM, the maximum uptake rate, Jmax, was 144.7 +/- 55.7 nmol/mg of protein/min and the nonsaturable first-order rate constant, Kd, was 6.66 +/- 1.98 microliters/mg of protein/min. At medium pH below 7.0, the uptake rate of [3H]acetic acid increased markedly with decreasing medium pH, whereas pH-independent uptake was observed in the presence of 10 mM acetic acid. An energy requirement for [3H]acetic acid uptake was also demonstrated, because metabolic inhibitors (2,4-dinitrophenol and rotenone) reduced significantly the uptake rate (P less than .05). Carbonylcyanide-p-trifluoro-methoxyphenylhydrazone, a protonophore, inhibited significantly the uptake of [3H]acetic acid at medium pH of 5.0 and 6.0, whereas 4,4'-diisothiocyanostilben-2,2'-disulfonic acid did not. Several MCAs inhibited significantly the uptake rate of [3H]acetic acid, whereas di- and tricarboxylic acids did not. The uptake of [3H]acetic acid was competitively inhibited by salicylic acid, with an inhibition constant, Ki, of 3.60 mM, suggesting a common transport system between acetic acid and salicylic acid. Moreover, at the medium pH of 7.4, salicylic acid and valproic acid inhibited significantly the uptake of [3H]acetic acid, demonstrating that the transport of MCA drugs could also be ascribed to the MCA transport system at the physiologic pH.(ABSTRACT TRUNCATED AT 250 WORDS)
Authors:
T Terasaki; S Takakuwa; S Moritani; A Tsuji
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  258     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1991 Sep 
Date Detail:
Created Date:  1991-10-17     Completed Date:  1991-10-17     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  932-7     Citation Subset:  IM    
Affiliation:
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.
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MeSH Terms
Descriptor/Qualifier:
3-O-Methylglucose
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid* / analogs & derivatives*
4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / analogs & derivatives,  pharmacology
Acetic Acid
Acetic Acids / pharmacokinetics
Amino Acids / pharmacology
Animals
Blood-Brain Barrier / physiology*
Brain / blood supply,  cytology,  metabolism
Capillaries / cytology,  metabolism
Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / pharmacology
Carboxylic Acids / pharmacokinetics*
Cattle
Cells, Cultured
Endothelium, Vascular / cytology,  metabolism*
Hydrogen-Ion Concentration
Leucine / pharmacokinetics
Methylglucosides / pharmacokinetics
Salicylic Acid
Salicylic Acids / pharmacology
Tritium / diagnostic use
Valproic Acid / pharmacology
Chemical
Reg. No./Substance:
0/Acetic Acids; 0/Amino Acids; 0/Carboxylic Acids; 0/Methylglucosides; 0/Salicylic Acids; 10028-17-8/Tritium; 146-72-5/3-O-Methylglucose; 27816-59-7/4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; 370-86-5/Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; 53005-05-3/4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; 61-90-5/Leucine; 61481-03-6/dihydro-DIDS; 64-19-7/Acetic Acid; 69-72-7/Salicylic Acid; 99-66-1/Valproic Acid

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


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