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Molecular analysis and structure-activity relationship modeling of the substrate/inhibitor interaction site of plasma membrane monoamine transporter.
J Pharmacol Exp Ther
November 2011
Department of Pharmaceutics, University of Washington, H272J Health Sciences Building, Seattle, WA 98195, USA.
Plasma membrane monoamine transporter (PMAT) is a new polyspecific transporter that interacts with a wide range of structurally diverse organic cations. To map the physicochemical descriptors of cationic compounds that allow interaction with PMAT, we systematically analyzed the interactions between PMAT and three series of structural analogs of known organic cation substrates including phenylalkylamines, n-tetraalkylammonium (n-TAA) compounds, and β-carbolines. Our results showed that phenylalkylamines with a distance between the aromatic ring and the positively charged amine nitrogen atom of ∼6.
View Article and Find Full Text PDFMolecular and functional characterization of an Na+-independent choline transporter in rat astrocytes.
J Neurochem
September 2005
Department of Pharmacology, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan.
In this study, we examined the molecular and functional characterization of choline uptake into cultured rat cortical astrocytes. Choline uptake into astrocytes showed little dependence on extracellular Na+. Na+-independent choline uptake was saturable and mediated by a single transport system, with an apparent Michaelis-Menten constant (Km) of 35.
View Article and Find Full Text PDFEvaluation of weak ion association between tetraalkylammonium ions and inorganic anions in aqueous solutions by capillary zone electrophoresis.
J Chromatogr A
January 2004
Department of Chemistry, Faculty of Science, Okayama University, 3-1-1 Tsushimanaka, Okayama 700-8530, Japan.
The evaluation of weak ion association between eleven (11) inorganic anions (charge -1 to -3) and five n-tetraalkylammonium ions, R4N+ (R: methyl, Me; ethyl, Et; propyl, Pr; butyl, Bu; pentyl, Am) in aqueous media at 25 degrees C was studied. The analysis of ion association equilibria was carried out under acidic condition (formate buffer, pH 3.5) at low separating potential (-10 kV) using a coated capillary with suppressed electroosmotic flow (micro = 4 x 10(-5) cm2 V(-1) s(-1)).
View Article and Find Full Text PDFInteractions of n-tetraalkylammonium compounds and biguanides with a human renal organic cation transporter (hOCT2).
Pharm Res
August 2002
Department of Biopharmaceutical Sciences, University of California, San Francisco, 94143-0446, USA.
Kinetic and selectivity differences between rodent, rabbit, and human organic cation transporters (OCT1).
J Pharmacol Exp Ther
March 2000
Department of Biopharmaceutical Sciences, University of California, San Francisco, California, USA.
Organic cation transporters play an important role in the absorption, distribution, and elimination of clinical agents, toxic substances, and endogenous compounds. In kidney preparations, significant differences in functional characteristics of organic cation transport between various species have been reported. However, the underlying molecular mechanisms responsible for these interspecies differences are not known.
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