Weak acid permeability through lipid bilayer membranes. Role of chemical reactions in the unstirred layer.

Walter, Anne; Hastings, David F.; Gutknecht, John

doi:10.1085/jgp.79.5.917

Cited by 60 publications

(21 citation statements)

References 15 publications

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“…This finding is in agreement with a recent fluorescence study (45) and previous suggestions (12,24). Most likely, the thick stratum corneum of the ruminal epithelium (32) creates an unstirred layer with a pH distinct from the bulk of the ruminal solution; this might play a role in the diffusional uptake of H-SCFA (24,45,75,93).…”

Section: Effect Of Scfa On the Intraepithelial Ph Of The Intact Ruminsupporting

confidence: 92%

“…These data thus confirm the presence of an apical microclimate above the transporting layer of cells (24,45,75,93). Lowering the mucosal pH has slow acidifying effects on the cytosolic pH.…”

Section: Microelectrode Experimentssupporting

confidence: 76%

“…Both diffusion of the protonated form (H-SCFA) (93) and uptake via SCFA Ϫ /HCO 3 Ϫ exchange with dissociation of CO 2 (5,24,78) should lead to an acidification of the cell (78), as shown in isolated cells of the ruminal epithelium in vitro (8). However, if, in intact tissue, the influx of SCFA is mediated by an anion exchanger (5) physically linked to NHE3 via scaffolding proteins (20) or if an influx of SCFA Ϫ anions occurs primarily via an apical anion channel similar to that mediating the basolateral efflux of acetate (85), cytosolic pH should remain constant or show a slight increase.…”

Section: Effect Of Scfa On the Intraepithelial Ph Of The Intact Ruminmentioning

confidence: 99%

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Modulation of urea transport across sheep rumen epithelium in vitro by SCFA and CO₂

Abdoun

Stumpff

Rabbani

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

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Urea transport across the gastrointestinal tract involves transporters of the urea transporter-B group, the regulation of which is poorly understood. The classical stimulatory effect of CO2 and the effect of short-chain fatty acids (SCFA) on the ruminal recycling of urea were investigated by using Ussing chamber and microelectrode techniques with isolated ruminal epithelium of sheep. The flux of urea was found to be phloretin sensitive and passive. At a luminal pH of 6.4, but not at 7.4, the addition of SCFA (40 mmol/l) or CO2/HCO 3 Ϫ (10% and 25 mmol/l) led to a fourfold increase in urea flux. The stepwise reduction of luminal pH in the presence of SCFA from 7.4 to 5.4 led to a bell-shaped modification of urea transport, with a maximum at pH 6.2. Lowering the pH in the absence of SCFA or CO2 had no effect. Inhibition of Na ϩ /H ϩ exchange increased urea flux at pH 7.4, with a decrease being seen at pH 6.4. In experiments with double-barreled, pH-sensitive microelectrodes, we confirmed the presence of an apical pH microclimate and demonstrated the acidifying effects of SCFA on the underlying epithelium. We confirm that the permeability of the ruminal epithelium to urea involves a phloretin-sensitive pathway. We present clear evidence for the regulation of urea transport by strategies that alter intracellular pH, with permeability being highest after a moderate decrease. The well-known postprandial stimulation of urea transport to the rumen in vivo may involve acute pH-dependent effects of intraruminal SCFA and CO2 on the function of existing urea transporters. pH i; urea transporter-B; short-chain fatty acids; microclimate; volatile fatty acid UREA, POSSIBLY BECAUSE OF its small size, was long thought to move passively across epithelia, depending only on the rate of delivery via blood. The urea permeability of cellular membranes has now been established to be several orders of magnitude above that of lipid membranes (11,92) and is coupled to the expression of specific urea-transporting proteins with channel-like kinetics (7,46,71,81,82,95). Whereas the role that these proteins play in the elegant renal concentrating mechanism has received much attention, their function and regulation in other parts of the body, such as the gut (39), continues to be poorly understood.In contrast to the paucity of our knowledge concerning extrarenal urea transport in humans, we have long known of the ability of camels, cows, or sheep to shift the excretion of urea from the kidney (62, 72) to the gastrointestinal tract (79). The transport of urea through the rumen epithelium was first demonstrated many years ago in vivo and in vitro (16,29,79,89) and the physiological significance is clear: in the rumen, dietary cellulose is broken down by bacteria that utilize ureanitrogen for the synthesis of microbial proteins. After passage into the duodenum, the amino acids of these proteins are absorbed and reach the liver, where new urea for secretion into the rumen can be formed. Recycling of nitrogen via urea secretion into the rumen thus ...

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Section: Effect Of Scfa On the Intraepithelial Ph Of The Intact Ruminsupporting

confidence: 92%

Section: Microelectrode Experimentssupporting

confidence: 76%

Section: Effect Of Scfa On the Intraepithelial Ph Of The Intact Ruminmentioning

confidence: 99%

See 1 more Smart Citation

Modulation of urea transport across sheep rumen epithelium in vitro by SCFA and CO₂

Abdoun

Stumpff

Rabbani

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…) that diffusion through the aqueous unstirred layers adjacent to the membrane is the rate-limiting step for diffusion across the membrane system (Walter et al, 1982). Given the high surface area available for transport processes, only small amounts of undissociated SCFA are necessary to maintain transport, and accordingly, widely diverse preparations such as snail neurons (Szatkowski and Thomas, 1989), ciliary epithelial cells of the eye (Helbig et al, 1989) or isolated cells of the ruminal epithelium (Bilk, 2008) are acidified by small amounts of SCFA.…”

mentioning

confidence: 99%

Transport of cations and anions across forestomach epithelia: conclusions from in vitro studies

Leonhard-Marek

Stumpff

Martens

2010

Animal

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Secretion of saliva as well as absorptive and secretory processes across forestomach epithelia ensures an optimal environment for microbial digestion in the forestomachs. Daily salivary secretion of sodium (Na 1 ) exceeds the amount found in plasma by a factor of 2 to 3, while the secretion of bicarbonate (HCO 3 2 ) is 6 to 8 times higher than the amount of HCO 3 2 in the total extracellular space. This implies a need for efficient absorptive mechanisms across forestomach epithelia to allow for an early recycling. While Na 1 is absorbed from all forestomachs via Na 1 /H 1 exchange and a non-selective cation channel that shows increased conductance at low concentrations of Mg 21 , Ca 21 or H 1 in the luminal microclima and at low intracellular Mg 21 , HCO 3 2 is secreted by the rumen for the buffering of ingesta but absorbed by the omasum to prevent liberation of CO 2 in the abomasum. Fermentation provides short chain fatty acids and ammonia (NH 3 ) that have to be absorbed both to meet nutrient requirements and maintain ruminal homeostasis of pH and osmolarity. The rumen is an important location for the absorption of essential minerals such as Mg 21 from the diet. Other ions can be absorbed, if delivered in sufficient amounts (Ca 21 , P i , K 1 , Cl 2 and NH 4 1 ). Although the presence of transport mechanisms for these electrolytes has been described earlier, our knowledge about their nature, regulation and crosstalk has increased greatly in the last years. New transport pathways have recently been added to our picture of epithelial transport across rumen and omasum, including an apical non-selective cation conductance, a basolateral anion conductance, an apical H 1 -ATPase, differently expressed anion exchangers and monocarboxylate transporters.Keywords: ruminants, sodium potassium magnesium and calcium, short chain fatty acids, chloride and bicarbonate, channels transporters and exchangers ImplicationsThe improved knowledge of ruminal ion transport clearly underlines its physiological meaning for the whole animal. For example, magnesium absorption is markedly reduced at low Mg and high K intake and the effect of potassium is diminished at high Mg intake. This variable interaction has been quantified recently permitting the prediction of Mg absorption. Great progress has also been made in understanding the interactions between the absorptive pathways for Na, short chain fatty acids and ammonium. The new findings on structure and regulation of various ion transporters will allow a better understanding of the challenges that different diets pose to the maintenance of homeostatic conditions within the rumen and within the cells of the surrounding epithelium, with the implications for the investigation of ruminal adaptation to different diets. Future studies on transport pathways should include the barrier function of rumen epithelium and its possible impairment under harsh feeding conditions.

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“…In contrast to lipid solubility, which increases by several magnitudes from acetate to decanoate, the dissociation constant (pK a ) in the C 2 -C 10 range is independent of the aliphatic chain length and approximately 4.8. Assuming an acid microclimate of pH 6.0-7.0 (18), it is unlikely that an unstirred layer will be limiting for a passive non-mediated diffusion process (19,20). Thus, if absorption is to be accounted for by a passive diffusional process, it should be proportional to the lipid solubility, which evidently is not the case (Table I).…”

Section: Discussionmentioning

confidence: 99%

Human Rectal Absorption of Short- and Medium-chain C₂-C₁₀Fatty Acids

Jørgensen

Holtug²,

Jeppesen³

et al. 1998

Scandinavian Journal of Gastroenterology

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Weak acid permeability through lipid bilayer membranes. Role of chemical reactions in the unstirred layer.

Cited by 60 publications

References 15 publications

Modulation of urea transport across sheep rumen epithelium in vitro by SCFA and CO₂

Modulation of urea transport across sheep rumen epithelium in vitro by SCFA and CO₂

Transport of cations and anions across forestomach epithelia: conclusions from in vitro studies

Human Rectal Absorption of Short- and Medium-chain C₂-C₁₀Fatty Acids

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Weak acid permeability through lipid bilayer membranes. Role of chemical reactions in the unstirred layer.

Cited by 60 publications

References 15 publications

Modulation of urea transport across sheep rumen epithelium in vitro by SCFA and CO2

Modulation of urea transport across sheep rumen epithelium in vitro by SCFA and CO2

Transport of cations and anions across forestomach epithelia: conclusions from in vitro studies

Human Rectal Absorption of Short- and Medium-chain C2-C10Fatty Acids

Contact Info

Product

Resources

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Modulation of urea transport across sheep rumen epithelium in vitro by SCFA and CO₂

Modulation of urea transport across sheep rumen epithelium in vitro by SCFA and CO₂

Human Rectal Absorption of Short- and Medium-chain C₂-C₁₀Fatty Acids