title: Diurnal rhythmicity in the transcription of jejunal drug transporters.
abstract: 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.
authors.affiliation: Department of Surgery, Brigham & Women's Hospital/Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
authors.forename: Adam T
authors.initials: AT
authors.lastname: Stearns
authors.forename: Anita
authors.initials: A
authors.lastname: Balakrishnan
authors.forename: David B
authors.initials: DB
authors.lastname: Rhoads
authors.forename: Stanley W
authors.initials: SW
authors.lastname: Ashley
authors.forename: Ali
authors.initials: A
authors.lastname: Tavakkolizadeh
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics*; D002940:Circadian Rhythm / Q000502:physiology*; D007583:Jejunum / Q000378:metabolism* / Q000502:physiology*; D008297:Male; D004364:Pharmaceutical Preparations / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D004364:Pharmaceutical Preparations; D012313:RNA
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