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 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.
Stearns
Adam T
AT
Department of Surgery, Brigham & Women's Hospital/Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
Balakrishnan
Anita
A
Rhoads
David B
DB
Ashley
Stanley W
SW
Tavakkolizadeh
Ali
A
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*
D002352:Carrier Proteins; D004364:Pharmaceutical Preparations; D012313:RNA
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