Increased Apical Insertion of the Multidrug Resistance Protein 2 (MRP2/ABCC2) in Renal Proximal Tubules following Gentamicin Exposure

Notenboom, Sylvia; Wouterse, Alfons C.; Peters, Bram; Kuik, L.H.; Heemskerk, Suzanne; Rüssel, Frans G. M.; Masereeuw, Rosalinde

doi:10.1124/jpet.106.104547

Cited by 21 publications

(18 citation statements)

References 36 publications

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“…It is well known that the proximal tubule is enriched in the expression of ATP-binding cassette (ABC) transporters [22][23][24][25]. In particular, the multiple organic anion transporters (MOATs) are expressed in abundance [22][23][24][25]. Their principal function is the secretion of large organic anions [22][23][24][25], of which ATP is a principal one.…”

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confidence: 99%

“…Upon chronic administration of a significant dose of one or more drugs in a human patient with a disease condition, the multidrug resistance (mdr) transporters [known as Pglycoprotein (PGP), etc.] will be upregulated and may also be a robust transporter conduit for ATP and other large anions [22][23][24][25]. This minireview does not revisit the debate concerning the role of ABC transporters in ATP transport and release; however, past reviews of this biology are cited here for interested parties [13-15, 26, 27].…”

mentioning

confidence: 99%

“…In particular, the multiple organic anion transporters (MOATs) are expressed in abundance [22][23][24][25]. Their principal function is the secretion of large organic anions [22][23][24][25], of which ATP is a principal one. Upon chronic administration of a significant dose of one or more drugs in a human patient with a disease condition, the multidrug resistance (mdr) transporters [known as Pglycoprotein (PGP), etc.]…”

mentioning

confidence: 99%

“…The classic example is para-amino hippurate (PAH), which is often used as a marker for PCT secretion [4][5][6]. It is well known that the proximal tubule is enriched in the expression of ATP-binding cassette (ABC) transporters [22][23][24][25]. In particular, the multiple organic anion transporters (MOATs) are expressed in abundance [22][23][24][25].…”

mentioning

confidence: 99%

“…Proximal-tubule-based large anion secretion Drug secretion and organic acid secretion also occur in the proximal tubule [22][23][24][25]. The classic example is para-amino hippurate (PAH), which is often used as a marker for PCT secretion [4][5][6].…”

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confidence: 99%

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Purinergic signaling in the lumen of a normal nephron and in remodeled PKD encapsulated cysts

Hovater

Olteanu

Welty

et al. 2008

Purinergic Signalling

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The nephron is the functional unit of the kidney. Blood and plasma are continually filtered within the glomeruli that begin each nephron. Adenosine 5′ triphosphate (ATP) and its metabolites are freely filtered by each glomerulus and enter the lumen of each nephron beginning at the proximal convoluted tubule (PCT). Flow rate, osmolality, and other mechanical or chemical stimuli for ATP secretion are present in each nephron segment. These ATP-release stimuli are also different in each nephron segment due to water or salt permeability or impermeability along different luminal membranes of the cells that line each nephron segment. Each of the above stimuli can trigger additional ATP release into the lumen of a nephron segment. Each nephron-lining epithelial cell is a potential source of secreted ATP. Together with filtered ATP and its metabolites derived from the glomerulus, secreted ATP and adenosine derived from cells along the nephron are likely the principal two of several nucleotide and nucleoside candidates for renal autocrine and paracrine ligands within the tubular fluid of the nephron. This minireview discusses the first principles of purinergic signaling as they relate to the nephron and the urinary bladder. The review discusses how the lumen of a renal tubule presents an ideal purinergic signaling microenvironment. The review also illustrates how remodeled and encapsulated cysts in autosomal dominant polycystic kidney disease (ADPKD) and remodeled pseudocysts in autosomal recessive PKD (ARPKD) of the renal collecting duct likely create an even more ideal microenvironment for purinergic signaling. Once trapped in these closed microenvironments, purinergic signaling becomes chronic and likely plays a significant epigenetic and detrimental role in the secondary progression of PKD, once the remodeling of the renal tissue has begun. In PKD cystic microenvironments, we argue that normal purinergic signaling within the lumen of the nephron provides detrimental acceleration of ADPKD once remodeling is complete.

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confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Purinergic signaling in the lumen of a normal nephron and in remodeled PKD encapsulated cysts

Hovater

Olteanu

Welty

et al. 2008

Purinergic Signalling

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Renal Transport of Organic Anions and Cations

Pelis

Wright

2011

Comprehensive Physiology

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Organic anions and cations (OAs and OCs, respectively) comprise an extraordinarily diverse array of compounds of physiological, pharmacological, and toxicological importance. The kidney, primarily the renal proximal tubule, plays a critical role in regulating the plasma concentrations of these organic electrolytes and in clearing the body of potentially toxic xenobiotics agents, a process that involves active, transepithelial secretion. This transepithelial transport involves separate entry and exit steps at the basolateral and luminal aspects of renal tubular cells. Basolateral and luminal OA and OC transport reflects the concerted activity of a suite of separate proteins arranged in parallel in each pole of proximal tubule cells. The cloning of multiple members of several distinct transport families, the subsequent characterization of their activity, and their subcellular localization within distinct regions of the kidney, now allows the development of models describing the molecular basis of the renal secretion of OAs and OCs. New information on naturally occurring genetic variation of many of these processes provides insight into the basis of observed variability of drug efficacy and unwanted drug-drug interactions in human populations. The present review examines recent work on these issues.

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Efflux Transporters in the Brain

Potschka¹,

Löscher²

2007

Handbook of Neurochemistry and Molecular Neurobiology

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Increased Apical Insertion of the Multidrug Resistance Protein 2 (MRP2/ABCC2) in Renal Proximal Tubules following Gentamicin Exposure

Cited by 21 publications

References 36 publications

Purinergic signaling in the lumen of a normal nephron and in remodeled PKD encapsulated cysts

Purinergic signaling in the lumen of a normal nephron and in remodeled PKD encapsulated cysts

Renal Transport of Organic Anions and Cations

Efflux Transporters in the Brain

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