The physiological role of drug transporters

Abstract

Transporters comprise the largest family of membrane proteins in human organism, including members of solute carrier transporter and ATP-binding cassette transporter families. They play pivotal roles in the absorption, distribution and excretion of xenobiotic and endogenous molecules. Transporters are widely expressed in various human tissues and are routinely evaluated during the process of drug development and approval. Over the past decade, increasing evidence shows that drug transporters are important in both normal physiology and disease. Currently, transporters are utilized as therapeutic targets to treat numerous diseases such as diabetes, major depression, hypertension and constipation. Despite the steady growth of the field of transporter biology, more than half of the members in transporter superfamily have little information available about their endogenous substrate(s) or physiological functions. This review outlines current research methods in transporter studies, and summarizes the drug-transporter interactions including drug-drug and drug-endogenous substrate interactions. In the end, we also discuss the therapeutic perspective of transporters based on their physiological and pathophysiological roles.

Control of metabolite efflux in microbial cell factories: current advances and future prospects

“…Traditionally, radio-isotopically labelled drugs would be used, but nowadays fluorescent assays (e.g. [216][217][218][219][220]) or mass spectrometric assays [221] are more common.…”

Rapid construction of a whole-genome mutant library by combining haploid stem cells and inducible self-inactivating PiggyBac transposon

“…More intriguingly, we also identified a few genes related to drug transportation in puromycin screening (Fig. 2F) (Liang et al, 2015). Moreover, GO analysis of puromycin resistant genes revealed that there was a significant enrichment in the terms of intracellular signal transduction, endocytosis, and components of the membrane (Figs.…”

Drug Metabolism in Preclinical Drug Development: A Survey of the Discovery Process, Toxicology, and Computational Tools

“…The alteration of ADME characteristics during inflammation can often be attributed to an enzymatic change in drug metabolism. The decrease in the expression of CYP450, which is the primary drug metabolizing enzyme in the liver, following inflammation would be an example of this [9]. …”

“…Tissue-specific extracts from liver or muscle can be utilized to investigate the role of a transporter in energy related metabolism [9]. Common transporters involved with the alteration of a drug’s ADME consists of P-gp, BCRP, OATP1B1/1B3, OAT1/3, OCT1 and OCT2 [10].…”

“…The unique expression level and transporting state of a transporter may be modified in relation to a systemic response ( i.e . immune response) to an exogenous or endogenous stimulant [9]. The alteration of compound ADME during inflammation can also be attributed to transporter changes in drug metabolism.…”