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What do drug transporters really do?
1Departments of Pediatrics, Medicine, and Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0693, USA.
Nature Reviews. Drug Discovery
|December 6, 2014
Summary
Drug transporters ATP-binding cassette (ABC) and solute carrier (SLC) families handle endogenous molecules, suggesting a role in remote sensing and signalling. This broadens understanding of drug interactions and disease mechanisms.
Area of Science:
- Pharmacology
- Physiology
- Biochemistry
Background:
- ATP-binding cassette (ABC) and solute carrier (SLC) transporters are crucial for drug disposition.
- Their endogenous roles in handling diverse physiological substrates are not fully understood.
- Understanding these roles is vital for predicting drug-drug interactions and drug effects.
Purpose of the Study:
- To review evidence for the endogenous functions of ABC and SLC transporters.
- To propose a broader role for these transporters in 'remote sensing and signalling'.
- To connect transporter functions to various disease mechanisms and drug effects.
Main Methods:
- Literature review and evidence synthesis.
- Discussion of transporter substrates including metabolites, nutrients, and signalling molecules.
- Conceptual framework development for 'remote sensing and signalling'.
Main Results:
- ABC and SLC transporters handle a wide array of endogenous compounds.
- Evidence supports a role for these transporters in intercellular and inter-organ communication.
- A "remote sensing and signalling" model is proposed for transporter functions.
Conclusions:
- ABC and SLC transporters play critical roles beyond drug transport, involved in endogenous signalling.
- This broader perspective aids in understanding drug-metabolite interactions and disease pathophysiology.
- Implications for drug development, disease mechanisms (e.g., diabetes, CKD), and development are highlighted.