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Nucleoside (and nucleobase) transporter proteins in the gut absorb nutrients and nucleoside-derived drugs. Their function and regulation are crucial for both nutrition and drug bioavailability, impacting purinergic signaling.

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Area of Science:

  • Gastrointestinal Physiology
  • Molecular Biology
  • Pharmacology

Background:

  • The gastrointestinal tract absorbs digested nucleosides and nucleobases via nucleoside (and nucleobase) transporter (NT) proteins.
  • NTs exhibit polarized expression in enterocytes, with concentrative nucleoside transporters (CNTs) on the apical side and equilibrative nucleoside transporters (ENTs) on the basolateral side.
  • While NT regulation is understood in animals, human intestinal NT function and nutritional modulation remain less clear due to limited cell models.

Purpose of the Study:

  • To review the physiological and pharmacological roles of nucleoside and nucleobase transporters in the gastrointestinal tract.
  • To explore the nutritional regulation of intestinal NTs.
  • To discuss the implications of NTs in the absorption of orally administered nucleoside- and nucleobase-derived drugs and potential drug-drug interactions.

Main Methods:

  • This review synthesizes existing research on intestinal NTs.
  • It examines data from animal models regarding nutritional regulation.
  • It discusses the role of NTs in drug absorption and bioavailability.

Main Results:

  • NT proteins are essential for absorbing nucleosides and nucleobases, key products of nucleoprotein digestion.
  • Adenosine, a bioactive nucleoside, modulates purinergic signaling within intestinal cells.
  • NTs influence the absorption of nucleoside-based drugs, affecting bioavailability and potentially causing drug-drug interactions.

Conclusions:

  • Nucleoside and nucleobase transporters play vital roles in nutrient absorption and the pharmacokinetics of related drugs.
  • Further research into human intestinal NT function is needed, particularly regarding nutritional influences.
  • Understanding NTs is critical for optimizing drug delivery and minimizing interactions in clinical practice.