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Involvement of multidrug resistance proteins (MDR) in the modulation of glucocorticoid response

Jeanette I Webster1, Jan Carlstedt-Duke

  • 1Department of Medical Nutrition, Karolinska Institute, Novum, Huddinge Hospital, Sweden. jwebster@codon.nih.gov

The Journal of Steroid Biochemistry and Molecular Biology
|February 19, 2003
PubMed

Insights

Glucocorticoid transport out of cells involves two distinct mechanisms: Abcb1a/Abcb1b and Abcc1a transporters. Understanding these pathways is crucial for addressing glucocorticoid resistance in various diseases.

Area of Science:

  • Cellular Biology
  • Pharmacology
  • Biochemistry

Background:

  • Glucocorticoid resistance poses a significant challenge in treating numerous diseases.
  • Cellular export of glucocorticoids, mediated by transport proteins, is a potential mechanism influencing treatment efficacy.
  • Multidrug resistance protein 1 (MDR1, ABCB1) is known to transport certain glucocorticoids.

Purpose of the Study:

  • To investigate the mechanisms of glucocorticoid transport in a mouse cell line (LMCAT).
  • To identify the specific transporters involved in glucocorticoid efflux.
  • To understand the diversity of transport mechanisms and their steroid specificity.

Main Methods:

  • Utilized a mouse cell line (LMCAT) sensitive to multidrug resistance protein inhibitors.
  • Assessed Abcb1a/Abcb1b transporter function by measuring rhodamine efflux inhibition.
  • Detected Abcc1a transporter function by observing the blockade of calcein transport with probenecid.
  • Confirmed the presence of Abcb1a, Abcb1b, and Abcc1a mRNA in the cells.

Main Results:

  • Identified two distinct glucocorticoid transport mechanisms in LMCAT cells.
  • Demonstrated that some glucocorticoids are transported by Abcb1a/Abcb1b transporters.
  • Showed that other glucocorticoids are transported by Abcc1a transporters.
  • Confirmed functional expression of both Abcb1a/Abcb1b and Abcc1a transporters.

Conclusions:

  • Glucocorticoid transport out of cells is mediated by at least two independent mechanisms: Abcb1a/Abcb1b and Abcc1a.
  • These transporters exhibit distinct steroid specificities, contributing to varied cellular responses.
  • This research provides critical insights into the molecular basis of glucocorticoid resistance.

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