Comparison of nonelectrolyte permeability patterns in several epithelia

Hingson, D.J.; Diamond, Jared M.

doi:10.1007/bf01867849

Cited by 49 publications

(12 citation statements)

References 48 publications

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“…The short chain-length fatty acids 4: 0, 5: 0, and 6: 0 manifest higher rates of uptake than would be anticipated from a linear extrapolation of the relationship for the longer chain-length fatty acids. Such deviant behavior has been found for a number of other low molecular-weight, very polar compounds in a variety of epithelial membranes, and may result from movement of these molecules through low-resistance shunt pathways between cells or because of some unusual permeability characteristic of the microvillus membrane itself (13,(25)(26)(27)(28)(29)(30). Uptake of the alcohols is much more rapid than the corresponding acids: however, the relative increase in permeation for the addition of each -CHO-group is the same up to decanol.…”

Section: Discussionmentioning

confidence: 93%

Delineation of the Dimensions and Permeability Characteristics of the Two Major Diffusion Barriers to Passive Mucosal Uptake in the Rabbit Intestine

Westergaard¹,

Dietschy²

1974

J. Clin. Invest.

270

151

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ABSTRA CT The rate of passive absorption into the intestinal mucosal cell is determined by at least two major diffusion barriers: an unstirred water layer and the cell membrane. This study defines the morphology and permeability characteristics of these two limiting structures. The unstirred water layer was resolved into two compartments: one behaves like a layer of water overlying the upper villi while the other probably consists of solution between villi. The superficial layer is physiologically most important during uptake of highly permeant compounds and varies in thickness from 115 to 334 Am as the rate of mixing of the bulk mucosal solution is varied. From data derived from a probe molecule whose uptake was limited by the unstirred layer, the effective surface area of this diffusion barrier also was determined to vary with stirring rate and equaled only 2.4 cm' 100 mg-' in the unstirred condition but increased to 11.3 cm' 100 mg-' with vigorous mixing. This latter value, however, was still only 1/170 of the anatomical area of the microvillus membrane. With these values, uptake rates for a number of passively absorbed probe molecules were corrected for unstirred layer resistance, and these data were used to calculate the incremental free energy changes associated with uptake of the -CH2-(-258 cal mol'), -OH (+ 564), and taurine (+ 1,463) groups. These studies, then, have defined the thickness and area of the un-

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Section: Discussionmentioning

confidence: 93%

Delineation of the Dimensions and Permeability Characteristics of the Two Major Diffusion Barriers to Passive Mucosal Uptake in the Rabbit Intestine

Westergaard¹,

Dietschy²

1974

J. Clin. Invest.

270

151

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“…The aqueous pore model, based on the violation by small polar solutes of Overton's rule, predicts passage of water and urea through the same pathway. Since the deviation from Overton's rule is very marked in erythrocytes and in rabbit gallbladder [26], and since phloretin dissociates the water and urea pathway in red cell membranes [37,40] it is an interesting observation that phloretin brings about the same effect in gallbladder membranes. This dissociation between the movement of water and urea undermines the aqueous pore model severely.…”

Section: Discussionmentioning

confidence: 98%

Dimensions of polar pathways through rabbit gallbladder epithelium

Jong

Slegers

1974

J. Membrain Biol.

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Summary. The permeability of rabbit gallbladder to hydrophilic nonelectrolytes, with molecular weights from 20 to 60,000, has]been studied. Restriction in the diffusion of the small electrolytes is very significant up to glycerol, which suggests permeation through aqueous pores with equivalent radii of 4/~. An extracellular pathway is responsible for the permeation of the larger solutes. This extracellular pathway shows no restriction in diffusion of molecules up to the size of inulin. Dextran (15,000 to 17,000 mol wt) is significantly restricted. Albumin permeability is < 10 .8 cm sec -1. These observations can be equated with equivalent pore radii of ~40 • for the shunt pathway.Increasing osmolarities of the incubation medium cause decreased cell-membrane permeability and increased shunt permeability. 0.5 mM phloretin induces a 60 % reduction in urea permeability and a 168 % increase in antipyrine permeability. No effect on the osmotic water permeability or on the shunt permeability is observed in the presence of phloretin. The apparent activation energy of urea permeation changes from values consistent with diffusion in bulk water, to values consistent with diffusion through hydrocarbon regions. This suggests that the polar route for urea permeation is blocked by phloretin.The contribution of the shunt pathway to osmotic flow induced by sucrose or NaC1 gradients is smaller than 16% according to Poiseuille's flow calculations. Tetraethylammoniumchloride and albumin have been shown to be osmotically more effective than sucrose, suggesting a greater shunt contribution to the total water flow.Extensive studies on nonelectrolyte permeability of rabbit gallbladder epithelium have led to the postulation of small aqueous pores in the cell membranes and a small number of larger pores somewhere in the epithelium [13,48,56]. In this respect gallbladder epithelium resembles the epithelium of kidney proximal tubules [5,23], stomach [1] and small intestine [33]. In all these tissues the anomalous permeability of relatively large hydrophilic solutes, such as sucrose, inulin and even bigger molecules, is explained by postulating the existence of some large aqueous pores in the epithelium.

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“…Special mention should be made in the case of urea, 0.A for this compound varies from 0 17 (very highly permeable) for the pancreas, to 9*98 (very impermeable) for the fish gall-bladder. Only for the dog small intestine is it similar to that of the pancreas (Hignson & Diamond, 1972). If the method described in this paper is valid then the pancreas is more permeable than gall-bladder and kidney proximal tubule to non-electrolyte molecules below a molecular volume of 85 cm3 mole-' and must therefore be classed along with these tissues as a 'leaky' epithelium.…”

Section: Compounds Which Had Anomalous Effectsmentioning

confidence: 94%

The permeability of the secretin stimulated exocrine pancreas to non‐electrolytes.

Dewhurst¹,

N²,

Hutson³

et al. 1978

The Journal of Physiology

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SUMMARY1. A method of measuring the permeability of the pancreas by determining the apparent reflexion coefficient (M-A) is described, in the isolated pancreas secreting maximally under the influence of secretin. The principle is to add a non-electrolyte to the perfusate which will create an osmotic gradient (RToEAC) counter to that of active transport and reduce the secretion rate. This is compared with the effect of an equal concentration (0-1 M) of sucrose (RTAC; oC = 1). The apparent reflection coefficient is obtained by dividing the percentage reduction in the secretion rate due to the test molecule with that due to sucrose.2. Sucrose when added to the perfusate inhibits pancreatic secretion. For every 10 mm increase in sucrose concentration, the secretion rate was inhibited by 7v1 %.It has been estimated that an osmotic gradient of 131 m-osmole/kg water will cause zero flow rate. This is a measure of the pressure required to counteract the local osmotic gradient set up by active transport, it is equivalent to about 3-4 atm.3. Non-electrolytes with molecular volumes greater than about 85 cm3 mole-' are relatively impermeable, below this value they enter the pancreatic juice with increasing ease as the molecular volume decreases.4. ovA for a number of compounds has been measured: urea 0-17; ethanediol 0-27; thiourea 0-51; glycerol 0*69; creatinine 0-81; erythritol 0-91; arabinose 0-96; xylose 0 98; sorbitol 0-98. 5. The addition of non-electrolytes to the perfusate had effects on pancreatic secretion which were a function of 0.A. For molecules with GJA lying between 0-81 and 1 0 an osmotic load of 0-1 M increased both the concentration of sodium plus potassium and the concentration of chloride plus bicarbonate by about 50 m-mole/l. Whereas the cation change is almost exclusively one of sodium that of the anions was preferentially an increase in chloride. For compounds with 0-A lying between 0 and 0-81 the concentration of sodium plus potassium was proportional to 0.A. 6. A number of compounds have been described which inhibit pancreatic secretion, other than by an osmotic effect. These include acetaldehyde, thioglycerol, nicotinamide, ribose, dihydroxyacetone, and glyceraldehyde.7. It is concluded that the pancreas is more permeable than the gall-bladder of rabbit, fish and bullfrog, the proximal tubule of the kidney of rat and the small intestine of bullfrog, but is probably similar to that of small intestine of guinea-pig and man.

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Comparison of nonelectrolyte permeability patterns in several epithelia

Cited by 49 publications

References 48 publications

Delineation of the Dimensions and Permeability Characteristics of the Two Major Diffusion Barriers to Passive Mucosal Uptake in the Rabbit Intestine

Delineation of the Dimensions and Permeability Characteristics of the Two Major Diffusion Barriers to Passive Mucosal Uptake in the Rabbit Intestine

Dimensions of polar pathways through rabbit gallbladder epithelium

The permeability of the secretin stimulated exocrine pancreas to non‐electrolytes.

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