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Research ArticleArticle

Neural Modulation of Cephalexin Intestinal Absorption Through the Di- and Tripeptide Brush Border Transporter of Rat Jejunum In Vivo

Françoise Berlioz, Stéphanie Julien, Annick Tsocas, Jacques Chariot, Claude Carbon, Robert Farinotti and Claude Rozé
Journal of Pharmacology and Experimental Therapeutics March 1999, 288 (3) 1037-1044;
Françoise Berlioz
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Stéphanie Julien
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Annick Tsocas
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Jacques Chariot
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Claude Carbon
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Robert Farinotti
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Claude Rozé
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Abstract

Intestinal absorption of β-lactamine antibiotics (e.g., cefixime and cephalexin) has been shown to proceed through the dipeptide carrier system. In a previous study, nifedipine (NFP), an L-type calcium channel blocker, enhanced the absorption of cefixime in vivo but not in vitro, and it was suggested that neural mechanisms might be involved in the effect of NFP. The aim of the present study was to assess the involvement of the nervous system on the intestinal absorption of cephalexin (CFX). To investigate this, we used a single-pass jejunal perfusion technique in rats. NFP and diltiazem enhanced approximately 2-fold the plasma levels of CFX in treated rats versus untreated controls. NFP also increased approximately 2-fold the CFX level in portal plasma and increased urinary excretion of CFX, thus indicating that CFX did effectively increase CFX intestinal absorption. Perfusing high concentrations of dipeptides in the jejunal lumen competitively reduced CFX absorption and inhibited the enhancement of CFX absorption produced by NFP. Hexamethonium and lidocaine inhibited the effect of NFP, whereas atropine, capsaicin, clonidine, and isoproterenol enhanced CFX absorption by the same order of magnitude as NFP. Thus, complex neural networks can modulate the function of the intestinal di- and tripeptide transporter. Sympathetic noradrenergic fibers, intestinal sensory neurons, and nicotinic synapses are involved in the increase of CFX absorption produced by NFP.

Footnotes

  • Send reprint requests to: C. Rozé, Institut National de la Santé et de la Recherche Médicale (INSERM) U410, 16 Rue H Huchard, 75870 Paris Cedex 18, France. E-mail:roze{at}bichat.inserm.fr

  • ↵1 This work was supported in part by Association Charles Debray.

  • Abbreviations:
    NFP
    nifedipine
    CFX
    cephalexin, KRB, Krebs-Ringer buffer solution
    HXM
    hexamethonium
    • Received March 23, 1998.
    • Accepted October 13, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 288 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 288, Issue 3
1 Mar 1999
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Research ArticleArticle

Neural Modulation of Cephalexin Intestinal Absorption Through the Di- and Tripeptide Brush Border Transporter of Rat Jejunum In Vivo

Françoise Berlioz, Stéphanie Julien, Annick Tsocas, Jacques Chariot, Claude Carbon, Robert Farinotti and Claude Rozé
Journal of Pharmacology and Experimental Therapeutics March 1, 1999, 288 (3) 1037-1044;

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Research ArticleArticle

Neural Modulation of Cephalexin Intestinal Absorption Through the Di- and Tripeptide Brush Border Transporter of Rat Jejunum In Vivo

Françoise Berlioz, Stéphanie Julien, Annick Tsocas, Jacques Chariot, Claude Carbon, Robert Farinotti and Claude Rozé
Journal of Pharmacology and Experimental Therapeutics March 1, 1999, 288 (3) 1037-1044;
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