Document Detail


L(+)- and D(-)-lactate modulate rat renal tubular accumulation of amantadine in the presence and absence of bicarbonate.
MedLine Citation:
PMID:  8531098     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effect of L(+)-, D(-)- and racemic (DL)-lactate on the energy-dependent renal uptake of the achiral organic cation amantadine was determined with purified proximal and distal cortical tubule fragments isolated from rat kidneys. Kinetic parameters for uptake of amantadine were measured, under constant pH, in bicarbonate buffer (Krebs-Henseleit [KHS]), and in lactate buffers (5 mM) with different proportions of the enantiomers. Km for amantadine uptake increased in all lactate buffers compared with KHS for both proximal and distal tubules. Km for uptake in DL-lactate was similar to that in D(-)-lactate for proximal tubules and to L(+)-lactate in distal tubules, but Km in L(+)-lactate was higher than in D(-)-lactate for both tubules. Maximal transport capacity (Vmax) in DL-lactate and mixtures of enantiomers were similar to KHS but higher than in pure L(+)- and D(-)-lactate. In KHS, lactate inhibited energy-dependent amantadine uptake in a biphasic manner. Graded competitive inhibition of amantadine uptake was observed between 1 and 15 mM lactate for both proximal and distal tubules. This first phase (1-15 mM) inhibited 60% of amantadine uptake. The second phase (15-20 mM lactate) showed a much steeper slope and inhibited the remaining amantadine uptake. There were no differences in inhibitory potencies of the lactate enantiomers for either proximal tubules or distal tubules amantadine tubule uptake. Our present studies suggest that L(+)- and D(-)-lactate modulate amantadine transport by interacting directly with the bicarbonate-dependent transport mechanism(s).
Authors:
M R Escobar; K Goralski; D S Sitar
Related Documents :
1562518 - Calciotropic hormones during reproduction.
1951778 - Is fetal acidosis in the human fetus maternogenic during labor? a reanalysis.
15152788 - Treatment of perinatal delusional disorder: a case report.
24700398 - "mild" vs. "long" protocol for controlled ovarian hyperstimulation in patients with exp...
21887038 - Management of paroxysmal hypertension due to incidental pheochromocytoma in pregnancy.
9021828 - Maternal serum alpha-fetoprotein and epithelial tumour marker concentrations are not in...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  275     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1995 Dec 
Date Detail:
Created Date:  1996-02-01     Completed Date:  1996-02-01     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:  1317-23     Citation Subset:  IM    
Affiliation:
Department of Pharmacology and Therapeutics, University of Mantiboa, Winnipeg, Canada.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Amantadine / metabolism,  pharmacokinetics*
Animals
Bicarbonates / metabolism*
Biological Transport
Kidney Tubules, Distal / drug effects*,  metabolism
Kidney Tubules, Proximal / drug effects*,  metabolism
Lactates / chemistry,  pharmacology*
Lactic Acid
Male
Rats
Rats, Sprague-Dawley
Chemical
Reg. No./Substance:
0/Bicarbonates; 0/Lactates; 50-21-5/Lactic Acid; 768-94-5/Amantadine

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


Previous Document:  Methylmercury acts at multiple sites to block hippocampal synaptic transmission.
Next Document:  Hemodynamic effects of acute and chronic treatment with aladotril, a mixed inhibitor of neutral endo...