Diurnal Rhythmicity in the Transcription of Jejunal Drug Transporters†

Diurnal Rhythmicity in the Transcription of Jejunal Drug Transporters†

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 t...

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Main Authors: Adam T. Stearns, Anita Balakrishnan, David B. Rhoads, Stanley W. Ashley, Ali Tavakkolizadeh
Format: Article
Language:English
Published: Elsevier 2008-01-01
Series:Journal of Pharmacological Sciences
Online Access:http://www.sciencedirect.com/science/article/pii/S1347861319313866
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spelling doaj-ae85e3d68e51418caf34b9c736d25b4f2020-11-25T01:26:21ZengElsevierJournal of Pharmacological Sciences1347-86132008-01-011081144148Diurnal Rhythmicity in the Transcription of Jejunal Drug Transporters†Adam T. Stearns0Anita Balakrishnan1David B. Rhoads2Stanley W. Ashley3Ali Tavakkolizadeh4Department 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, UKDepartment 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, UKPediatric Endocrine Unit, MassGeneral Hospital for Children / Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USADepartment of Surgery, Brigham & Women’s Hospital / Harvard Medical School, 75 Francis Street, Boston, MA 02115, USADepartment of Surgery, Brigham & Women’s Hospital / Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA; Corresponding author. atavakkoli@partners.orgIntestinal 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 transporterhttp://www.sciencedirect.com/science/article/pii/S1347861319313866
collection DOAJ
language English
format Article
sources DOAJ
author Adam T. Stearns
Anita Balakrishnan
David B. Rhoads
Stanley W. Ashley
Ali Tavakkolizadeh
spellingShingle Adam T. Stearns
Anita Balakrishnan
David B. Rhoads
Stanley W. Ashley
Ali Tavakkolizadeh
Diurnal Rhythmicity in the Transcription of Jejunal Drug Transporters†
Journal of Pharmacological Sciences
author_facet Adam T. Stearns
Anita Balakrishnan
David B. Rhoads
Stanley W. Ashley
Ali Tavakkolizadeh
author_sort Adam T. Stearns
title Diurnal Rhythmicity in the Transcription of Jejunal Drug Transporters†
title_short Diurnal Rhythmicity in the Transcription of Jejunal Drug Transporters†
title_full Diurnal Rhythmicity in the Transcription of Jejunal Drug Transporters†
title_fullStr Diurnal Rhythmicity in the Transcription of Jejunal Drug Transporters†
title_full_unstemmed Diurnal Rhythmicity in the Transcription of Jejunal Drug Transporters†
title_sort diurnal rhythmicity in the transcription of jejunal drug transporters†
publisher Elsevier
series Journal of Pharmacological Sciences
issn 1347-8613
publishDate 2008-01-01
description 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
url http://www.sciencedirect.com/science/article/pii/S1347861319313866
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AT davidbrhoads diurnalrhythmicityinthetranscriptionofjejunaldrugtransporters
AT stanleywashley diurnalrhythmicityinthetranscriptionofjejunaldrugtransporters
AT alitavakkolizadeh diurnalrhythmicityinthetranscriptionofjejunaldrugtransporters
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