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P-glycoprotein and bilirubin disposition
J F Watchko1, M J Daood, B Mahmood
1Division of Neonatology and Developmental Biology, Department of Pediatrics, University of Pittsburgh School of Medicine, Magee-Womens Research Institute, 300 Halket Street, Pittsburgh, PA 15213, USA.
Summary
Unconjugated bilirubin may be a substrate for P-glycoprotein (Pgp), an efflux pump at the blood-brain barrier. Pgp
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- P-glycoprotein (Pgp) is an ATP-dependent efflux pump found on brain capillary endothelial cells and astrocytes.
- Pgp limits the entry of lipophilic substances into the central nervous system.
- Understanding Pgp's role is crucial for drug delivery and understanding substance disposition in the brain.
Purpose of the Study:
- To review evidence on unconjugated bilirubin as a Pgp substrate.
- To examine the developmental expression of Pgp at the blood-brain barrier and gastrointestinal tract.
- To provide insights into bilirubin disposition in immature individuals.
Main Methods:
- Literature review of existing studies.
- Analysis of Pgp expression patterns during development.
- Assessment of bilirubin's interaction with Pgp.
Main Results:
- Evidence suggests unconjugated bilirubin may be transported by Pgp.
- Pgp expression at the blood-brain barrier and gut epithelium shows developmental changes.
- These findings correlate with potential differences in bilirubin handling in neonates.
Conclusions:
- Unconjugated bilirubin's potential as a Pgp substrate warrants further investigation.
- Ontogeny of Pgp influences bilirubin disposition, particularly in immature subjects.
- This has implications for understanding conditions like neonatal jaundice and kernicterus.