Effects of membrane potential and surface potential on the kinetics of solute transport

Barts, P.W.J.A.; Borst-Pauwels, G.W.F.H.

doi:10.1016/0005-2736(85)90344-x

Cited by 10 publications

(9 citation statements)

References 26 publications

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“…20 Although well-known as a determinant of passive ion transport (Barts and Borst-Pauwels, 1985;Stein, 1977), this phenomenon is not accounted for in conventional models applied to the OCT mediated transport of drugs. In these conventional models, the rate of drug transport is defined as a first order process (Hsu et al, 2014) or by a Michaelis-Menten function when saturation is observed at higher substrate concentrations (Jamei et al, 2014;Neuhoff et al, 2013b).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Metformin and cimetidine: Physiologically based pharmacokinetic modelling to investigate transporter mediated drug–drug interactions

Burt

Neuhoff

Almond

et al. 2016

European Journal of Pharmaceutical Sciences

100

131

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Metformin is used as a probe for OCT2 mediated transport when investigating possible DDIs with new chemical entities. The aim of the current study was to investigate the ability of physiologically-based pharmacokinetic (PBPK) models to simulate the effects of OCT and MATE inhibition by cimetidine on metformin kinetics. PBPK models were developed, incorporating mechanistic kidney and liver sub-models for metformin (OCT and MATE substrate) and a mechanistic kidney sub-model for cimetidine. The models were used to simulate inhibition of the MATE1, MATE2-K, OCT1 and OCT2 mediated transport of metformin by cimetidine. Assuming competitive inhibition and using cimetidine Ki values determined in vitro, the predicted metformin AUC ratio was 1.0 compared to an observed value of 1.46. The observed AUC ratio could only be recovered with this model when the cimetidine Ki for OCT2 was decreased 1000-fold or the Ki's for both OCT1 and OCT2 were decreased 500-fold. An alternative description of metformin renal transport by OCT1 and OCT2, incorporating electrochemical modulation of the rate of metformin uptake together with 8-18-fold decreases in cimetidine Ki's for OCTs and MATEs, allowed recovery of the extent of the observed effect of cimetidine on metformin AUC. While the final PBPK model has limitations, it demonstrates the benefit of allowing for the complexities of passive permeability combined with active cellular uptake modulated by an electrochemical gradient and active efflux.

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Section: Accepted Manuscriptmentioning

confidence: 99%

Metformin and cimetidine: Physiologically based pharmacokinetic modelling to investigate transporter mediated drug–drug interactions

Burt

Neuhoff

Almond

et al. 2016

European Journal of Pharmaceutical Sciences

100

131

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“…As a consequence of the cell wall properties of roots, ionic relations in the vicinity of the plasmalemma can vary considerably from those in the rhizosphere (Franklin, 1969; Grignon & Sentenac, 1991). Such phenomena are of fundamental importance for the understanding of processes such as ionic antagonisms (Borst‐Pauwels & Severens, 1984; Barts & Borst‐Pauwels, 1985; Collier & O’Donnell, 1997) or apparent synergisms such as those between Ca 2+ and H 2 PO 4 − (Franklin, 1969). However, ionic gradients can arise not only as a result of apoplastic properties or ion uptake (Kochian & Lucas, 1982; Henriksen et al.…”

Section: The Root Apoplast – Nutrient Uptake and Short‐distance mentioning

confidence: 99%

The apoplast and its significance for plant mineral nutrition

2001

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SummaryIt has only recently become apparent that the apoplast plays a major role in a diverse range of processes, including intercellular signalling, plant-microbe interactions and both water and nutrient transport. Broadly defined, the apoplast constitutes all compartments beyond the plasmalemma -the interfibrillar and intermicellar space of the cell walls, and the xylem, including its gas-and water-filled intercellular space -extending to the rhizoplane and cuticle of the outer plant surface. The physicochemical properties of cell walls influence plant mineral nutrition, as nutrients do not simply pass through the apoplast to the plasmalemma but can also be adsorbed or fixed to cell-wall components. Here, current progress in understanding the significance of the apoplast in plant mineral nutrition is reviewed. The contribution of the root apoplast to short-distance transport and nutrient uptakes is examined particularly in relation to Na + toxicity and Al 3+ tolerance. The review extends to long-distance transport and the role of the apoplast as a habitat for microorganisms. In the leaf, the apoplast might have benefits over the vacuole as a site for short-term nutrient storage and solute exchange with the atmosphere.

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“…The Vmax depends on the number of translocator sites per g protein and the rate coefficient of translocation of the carrier across the membrane (14). The latter is a function of several factors including the electrical charge on the loaded and unloaded carrier and the composition of the lipid microenvironment (14,15). The results herein do not distinguish between these possibilities.…”

Section: Resultsmentioning

confidence: 61%

“…Kinetic analyses were performed under voltage-clamped conditions to minimize effects of electrical potential difference on taurine transport (15). The diffusional component of taurine transport as measured with a KC1 gradient was similar using membrane vesicles from either age group.…”

Section: Resultsmentioning

confidence: 99%

Enhanced Uptake of Taurine by Basolateral Plasma Membrane Vesicles Isolated from Developing Rat Liver

1988

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ABSTRACT. Inasmuch as taurine biosynthesis is decreased during early postnatal life, an efficient mechanism for taurine uptake by the liver must be present to maintain intracellular stores of this &amino acid. Therefore, basolateral liver plasma vesicles prepared from 14-day and adult rats were used to examine taurine transport during development. For both age groups, the presence of an inwardly directed Na+ gradient stimulated the initial rate of taurine uptake and caused a transient accumulation of taurine above equilibrium. For all time points before equilibrium, taurine uptake was significantly greater with membrane vesicles from 14-day compared to adult rat livers. In contrast, no age-related differences in Na+-independent uptake as measured with a K+ gradient were detected. With equal intravesicular and extravesicular Na+ concentrations, taurine uptake remained significantly greater in the younger age group. For both age groups, Na+-dependent taurine uptake was saturable but the apparent Km and Vmax for Na+-dependent taurine uptake were significantly greater in membrane vesicles from 14-day compared to adult rats. These findings suggest that an increased number of functional carriers for taurine are present in developing compared to adult basolateral plasma membrane perhaps reflecting the needs of the immature liver for this essential nutrient. (Pediatr Res 23: 172-175,1988) Abbreviations HEPES, N-2 hydroxyethylpiperazine-N-2-ethanesulfonic acid LPMV, liver plasma membrane vesicles LPM, liver plasma membrane CSAD, cysteine sulfinic acid decarboxylase Taurine is the major free intracellular amino acid present in most tissues (1). Conjugation of bile acids with this @-amino acid has been well established and the proportion of taurine conjugates present in bile depends on species, stage of development, and substrate availability. Taurine may also participate in osmoregulation of cell volume and control of membrane excitability (2, 3).

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Effects of membrane potential and surface potential on the kinetics of solute transport

Cited by 10 publications

References 26 publications

Metformin and cimetidine: Physiologically based pharmacokinetic modelling to investigate transporter mediated drug–drug interactions

Metformin and cimetidine: Physiologically based pharmacokinetic modelling to investigate transporter mediated drug–drug interactions

The apoplast and its significance for plant mineral nutrition

Enhanced Uptake of Taurine by Basolateral Plasma Membrane Vesicles Isolated from Developing Rat Liver

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