Diurnal Rhythmicity in the Transcription of Jejunal Drug Transporters†

Adam T. Stearns; Anita Balakrishnan; David B. Rhoads; Stanley W. Ashley; Ali Tavakkolizadeh

Journal of Pharmacological Sciences (Jan 2008)

Diurnal Rhythmicity in the Transcription of Jejunal Drug Transporters†

Adam T. Stearns,
Anita Balakrishnan,
David B. Rhoads,
Stanley W. Ashley,
Ali Tavakkolizadeh

Affiliations

Adam T. Stearns: Department of Surgery, Brigham & Women’s Hospital / Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA; Department of Physiology, Anatomy & Genetics, University of Oxford, South Parks Road, Oxford, OX1 3QX, UK
Anita Balakrishnan: Department of Surgery, Brigham & Women’s Hospital / Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA; School of Clinical Sciences, Division of Gastroenterology, University of Liverpool, Crown Street, Liverpool, L69 3GE, UK
David B. Rhoads: Pediatric Endocrine Unit, MassGeneral Hospital for Children / Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA
Stanley W. Ashley: Department of Surgery, Brigham & Women’s Hospital / Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
Ali Tavakkolizadeh: Department of Surgery, Brigham & Women’s Hospital / Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA; Corresponding author. [email protected]

Journal volume & issue: Vol. 108, no. 1
pp. 144 – 148

Abstract

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Intestinal drug efflux proteins play a major role in the pharmacokinetics of many drugs. We assessed diurnal rhythmicity in the expression of ten major drug transporters. We acquired male Sprague-Dawley rats and harvested jejunal mucosa at 3-h intervals across a 24-h period. qPCR was performed for ten transporters: Mdr1, Mdr3, Mrp1 – 3, Mct1, Brcp, Pept1, Octn2, and Oatp-b. Rhythmicity was assessed with the cosinor procedure. Diurnal rhythmicity was observed for Mdr1, Mct1, Mrp2, Pept1, and Bcrp (1.6 – 5.4-fold-changes). Acrophases occurred during fasting hours. We conclude that many drug transporters display profound diurnal rhythms in transcription, which may underlie diurnal rhythms in drug pharmacokinetics. Keywords:: diurnal rhythm, intestinal, drug efflux transporter

Published in Journal of Pharmacological Sciences

ISSN: 1347-8613 (Print)
Publisher: Elsevier
Country of publisher: Japan
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://www.journals.elsevier.com/journal-of-pharmacological-sciences

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