Analysis of membrane transport mechanisms of endogenous substrates using chromatographic techniques

Abstract

Membrane transporters are expressed in various bodily tissues and play essential roles in the homeostasis of endogenous substances and the absortion, distribution and/or excretion of xenobiotics. For transporter assays, radioisotope-labeled compounds have been mainly used. However, commercially available radioisotopelabeled compounds are limited in number and relatively expensive. Chromatographic analyses such as high-performance liquid chromatography with ultraviolet absorptiometry and liquid chromatography with tandem mass spectrometry have also been applied for transport assays. To elucidate the transport properties of endogenous substrates, although there is no difficulty in performing assays using radioisotope-labeled probes, the endogenous background and the metabolism of the compound after its translocation across cell membranes must be considered when the intact compound is assayed. In this review, the current state of knowledge about the transport of endogenous substrates via membrane transporters as determined by chromatographic techniques is summarized. Chromatographic techniques have contributed to our understanding of the transport of endogenous substances including amino acids, catecholamines, bile acids, prostanoids and uremic toxins via membrane transporters.

Porous gold-layered cubic and octahedral Cu-oxide nanocrystals: Dopamine sensing

“…Numerous reports are available on potential methods to be used for the determination of DA concentrations, these include spectroscopic, 5,6 chromatographic, 7–9 and electrochemical sensing. 6,10–12 Of these various methods, electrochemical sensing offers rapid, effective and efficient testing with low detection limits. 13–15 During the electrochemical oxidation of DA, dopaminoquinone is formed through a one-step two-electron transfer process.…”

“…6,10–12 Of these various methods, electrochemical sensing offers rapid, effective and efficient testing with low detection limits. 13–15 During the electrochemical oxidation of DA, dopaminoquinone is formed through a one-step two-electron transfer process. 16 This process, however, this is not reproducible on bare electrodes.…”

Bile Acid–Drug Interaction via Organic Anion-Transporting Polypeptide 4C1 Is a Potential Mechanism of Altered Pharmacokinetics of Renally Excreted Drugs

“…OATP4C1 is the only member of the OATP family expressed in the kidneys. It localizes to the basolateral membrane of the renal proximal tubular cells and is involved in the excretion of thyroid hormone [ 29 ], cyclic adenosine monophosphate [ 29 ], uremic toxins [ 30 , 31 , 32 , 33 ], cardiac glycosides (ouabain and digoxin) [ 29 , 34 , 35 ], methotrexate [ 29 ], and sitagliptin [ 36 ] into the urine. We have previously shown that 10 drugs, namely, nicardipine, spironolactone, fluvastatin, crizotinib, levofloxacin, clarithromycin, ritonavir, saquinavir, quinidine, and verapamil, strongly inhibited OATP4C1 [ 37 ].…”