Browsing by Author "Boyer, JL"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Down-regulation of the Na+/taurocholate cotransporting polypeptide during pregnancy in the rat
    (ELSEVIER SCIENCE BV, 2003) Arrese, M; Traumer, M; Ananthanarayanan, M; Pizarro, M; Solis, N; Accatino, L; Soroka, C; Boyer, JL; Karpen, SJ; Miquel, JF; Suchy, FJ
    Background: Experimental studies have shown decreased bile acid (BA) uptake and reduced excretion of cholephilic compounds in pregnant rodents.
  • No Thumbnail Available
    Item
    The hypolipidemic drug metabolites nafenopin-CoA and ciprofibroyl-CoA are competitive P2Y1 receptor antagonists
    (2003) Coddou, C; Loyola, G; Boyer, JL; Bronfman, M; Huidobro-Toro, JP
    Coenzyme A (CoA-SH), endogenous and drug-derived CoA-derivatives were tested as putative antagonists of P2Y receptors expressed in Xenopus laevis oocytes, a method used to determine calcium-activated chloride current, an indicator of the activation of these receptors. CoA-SH antagonized reversibly and in a concentration-dependent manner the ATP-gated currents evoked by the human P2Y(1) but not the P2Y(2) receptor. Palmitoyl-CoA was four-fold more potent than CoASH as an antagonist while palmitoyl-carnitine was inactive, highlighting the role of the CoA-SH moiety in the antagonism. The CoA derivatives of nafenopin and ciprofibrate, two clinically relevant hypolipidemic drugs, increased 13 and three-fold the potency of CoA-SH, respectively. The K(B)s of nafenopin-CoA and ciprofibroyl-CoA were 58 and 148 nM, respectively; the slopes of the Schild plots were unitary. Neither 100 muM nafenopin nor ciprofibrate alone altered the P2Y, receptor activity. Neither CoA-SH nor ciprofibroyl-CoA antagonized the rat P2X(2) or the P2X(4) nucleotide receptors nor interacted with the 5-HT2A/C receptors. The bulky drug CoA-SH derivatives identify a hydrophobic pocket, which may serve as a potential target for novel selective P2Y(1) antagonists. (C) 2003 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.