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Research ArticleArticle

Substrate Specificity of Organic Cation/H+ Exchange in Avian Renal Brush-Border Membranes

A. R. Villalobos and E. J. Braun
Journal of Pharmacology and Experimental Therapeutics December 1998, 287 (3) 944-951;
A. R. Villalobos
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E. J. Braun
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Abstract

The substrate specificity of the avian renal organic cation exchanger was examined in isolated renal brush-border membrane vesicles. Endobiotic and xenobiotic organic cations (OCs) were tested at a concentration of 100 μM for cis-inhibition of14C-tetraethylammonium (TEA)/H+ exchange and at 1 mM for trans-stimulation of 14C-TEA efflux. The xenobiotic cations amiloride, cimetidine, mepiperphenidol, procainamide, quinidine, quinine, and ranitidinecis-inhibited TEA uptake ≥ 80%; isoproterenol and unlabeled TEA inhibited uptake at least 30%. In contrast, the endogenous cations acetylcholine, choline, and guanidine did not inhibit TEA uptake; however, epinephrine, N1-methylnicotinamide, serotonin, and thiamine inhibited uptake as much as 60%. Each endogenous cation, except thiamine,trans-stimulated TEA efflux, and xenobiotic cations, excluding isoproterenol and TEA, trans-inhibited TEA efflux. The data suggest that the avian renal tubule luminal OC exchanger has greater affinity for xenobiotic cations than for endobiotic cations, but greater transport capacity for endobiotics than for xenobiotics.

Footnotes

  • Send reprint requests to: Alice R. Villalobos, Ph.D., Department of Physiology and Neurobiology, Box U-156, 3107 Horsebarn Hill Rd., University of Connecticut, Storrs, CT 06269-4156. E-mail:villalobos{at}oracle.pnb.uconn.edu

  • Abbreviations:
    OC
    organic cation
    TEA
    tetraethylammonium
    NMN
    N1-methylnicotinamide
    Darstine
    mepiperphenidol
    BBMV
    brush-border membrane vesicle
    Km
    Michaelis constant
    Vmax
    maximal rate of uptake
    Vmaxapp
    apparent maximal rate of uptake
    Kmapp
    apparentKm
    Ki
    calculated inhibitor constant
    pKa
    dissociation constant
    M.W.
    molecular weight
    Tm
    maximum tubular transport rate
    • Received January 5, 1998.
    • Accepted June 24, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 287, Issue 3
1 Dec 1998
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Research ArticleArticle

Substrate Specificity of Organic Cation/H+ Exchange in Avian Renal Brush-Border Membranes

A. R. Villalobos and E. J. Braun
Journal of Pharmacology and Experimental Therapeutics December 1, 1998, 287 (3) 944-951;

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Research ArticleArticle

Substrate Specificity of Organic Cation/H+ Exchange in Avian Renal Brush-Border Membranes

A. R. Villalobos and E. J. Braun
Journal of Pharmacology and Experimental Therapeutics December 1, 1998, 287 (3) 944-951;
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