Routes of nonelectrolyte permeability in gallbladder. Effects of 2,4,6-triaminopyrimidinium (TAP).

Moreno, Julio H.

doi:10.1085/jgp.66.1.117

Cited by 28 publications

(18 citation statements)

References 7 publications

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“…TAP had no effect on either PEG permeability or absorptive water flux (Table1); this observation neither supports nor opposes our conclusions, but this lack of effect is by no means unprecedented. For example, in rabbit and frog gall bladder preparations, where there was strong evidence for paracellular permeability to several small molecules, TAP did not affect net water or Cl -flux rates, or the permeability to sucrose, a molecule of comparable size to PEG-400 (Moreno, 1975). The author concluded that water was permeating mainly via the transcellular route.…”

Section: Discussion Overviewmentioning

confidence: 99%

Independence of net water flux from paracellular permeability in the intestine ofFundulus heteroclitus, a euryhaline teleost

Wood

Grosell

2012

Journal of Experimental Biology

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SUMMARYParacellular permeability and absorptive water flux across the intestine of the euryhaline killifish were investigated using in vitro gut sac preparations from seawater-and freshwater-acclimated animals. The permeability of polyethylene glycol (PEG), a wellestablished paracellular probe, was measured using trace amounts of radiolabelled oligomers of three different molecular sizes (PEG-400, PEG-900 and PEG-4000) at various times after satiation feeding. All three PEG molecules were absorbed, with permeability declining as a linear function of increasing hydrodynamic radius. Response patterns were similar in seawater and freshwater preparations, though water absorption and PEG-900 permeability were greater in the latter. Despite up to 4-fold variations in absorptive water flux associated with feeding and fasting (highest at 1-3h, lowest at 12-24h and intermediate at 1-2weeks post-feeding), there were no changes in PEG permeability for any size oligomer. When PEG permeability was measured in the opposite direction (i.e. serosal to mucosal) from net water flux, it was again unchanged. HgCl 2 (10 -3 moll -1 ), a putative blocker of aquaporins, eliminated absorptive water flux yet increased PEG-4000 permeability by 6-to 8-fold in both freshwater and seawater preparations. Experimentally raising the serosal osmolality by addition of 300mmoll -1 mannitol increased the absorptive water flux rate 10-fold, but did not alter PEG permeability. Under these conditions, HgCl 2 reduced absorptive water flux by 60% and again increased PEG permeability by 6-to 8-fold in both freshwater and seawater preparations. Clearly, there was no influence of solvent drag on PEG movement. The putative paracellular blocker 2,4,6-triaminopyrimidine (TAP, 20mmoll -1 ) had no effect on net water flux or PEG permeability. We conclude that PEG and water move by separate pathways; absorptive water transport probably occurs via a transcellular route in the intestine of Fundulus heteroclitus.

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Section: Discussion Overviewmentioning

confidence: 99%

Independence of net water flux from paracellular permeability in the intestine ofFundulus heteroclitus, a euryhaline teleost

Wood

Grosell

2012

Journal of Experimental Biology

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“…Previous work, however, suggests that the situation is quite different in the rabbit gall-bladder. In that epithelium, although a significant sucrose permeability is evident in the absence of fluid transport (1-8 x 10-6 cm sec', Moreno, 1975b), relatively little sucrose appears in the absorbate during fluid transport (Diamond, 1964b).…”

Section: Discussionmentioning

confidence: 99%

“…The second of these three routes was attributed initially to a polar pathway through the epithelial cell membranes (Wright & Diamond, 1969). More recently though, Moreno (1975b) has demonstrated that 2,4,6-triaminopyrimidinium (TAP), which blocks the paracellular cation channels, also reduces the permeability to small polar non-electrolytes, so there may in addition, or alternatively, be a substantial paracellular permeability to these smaller molecules.…”

Section: Discussionmentioning

confidence: 99%

Paracellular non‐electrolyte permeation during fluid transport across rabbit gall‐bladder epithelium

Steward

1982

The Journal of Physiology

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SUMMARY1. Mucosa-to-serosa fluxes of seven polar non-electrolytes were determined during isotonic fluid transport across the unilateral rabbit gall-bladder preparation in an attempt to estimate the contribution of the paracellular pathway to the total transepithelial water flow.2. 3H-and '4C-labelled non-electrolyte tracers appeared in the transported fluid at fractions (f,) of their mucosal concentration which were inversely related to molecular size: ethanediol, 0-80; thiourea, 0-55; glycerol, 0-16; erythritol, 0-11; mannitol, 0-05; sucrose, 0-05; inulin, 0-02. The mean volume flow rate was 78 #l . cm-2 hr-1.3. While the fluxes of the larger molecules were probably due to diffusion through a small but unrestricted paracellular 'shunt' permeability, the highf. values obtained for the smaller molecules indicate the existence of a substantial paracellular permeability restricted to molecules smaller than erythritol.4. Upper limits to the transcellular ethanediol and thiourea permeabilities, estimated from the time constants oftracer efflux from preloaded epithelial cells, were too low to account for more than a very small fraction of the transepithelial fluxes observed in the unilateral preparation.5. Comparison of the Af values with the predictions of a hydrodynamic model of paracellular permeation suggests that in order to account for the large fluxes of ethanediol and thiourea, considerably more than one half of the transepithelial water flow must follow the paracellular pathway.6. Following a reduction of the mucosal osmolality to 110 m-osmole kg-1, the apparent non-electrolyte permeability of the epithelium increased steadily over a period of 4 hr. This seems to reflect an increase in the shunt permeability rather than a change in the selectivity of the restricted permeability. 7. It is concluded that during isotonic fluid transport the bulk of the transepithelial water flow crossing the epithelium passes through paracellular channels of approximately 3 A radius which are probably located in the intercellular junction.

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“…No direct or reliable method to approach this question exists at present. Some authors cite indirect evidence to support a predominantly transcellular route for leaky epithelia (e.g., Wright etal., 1972;van Os & Slegers, 1973;Moreno, 1975;van Os et al, 1979). Other authors cite indirect evidence to support a predominantly transjunctional route (e.g., Sackin & Boulpaep, 1975;Fischbarg et al, 1977;Hill & Hill, 1978a and b).…”

Section: Transeellular Vs Transjunctional Route Of Water Flowmentioning

confidence: 99%

Osmotic water flow in leaky epithelia

1979

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I review three currently unsolved and controversial problems in understanding solute-linked water transport in epithelia. 1. Values of osmotic water permeability (Posm) calculated from steady-state osmotic flow in response to a gradient of a probe molecule tend to be underestimates, because of three unstirred-layer (USL) effects. These are: dissipation of the probe's gradient by diffusion in USL's; reduction of the probe's gradient, due to the sweeping-away effect of water flow generated by the probe itself; and solute polarization (creation of an opposing gradient of an initially symmetrically distributed solute by the sweeping-away effect). These errors increase with probe permeability, USL thickness, Posm, and concentration ratio of symmetrically distributed solute to probe, and vary inversely as the fractional area available for water flow (e.g., lateral intercellular space width). The form of an osmotic transient, and the possibility of extracting a true Posm value from the transient, depend on the relative values of three time constants: those for solute diffusion in USL's, for solute polarization by water flow in USL's and for measuring water flow. Sweeping-away effects cause major underestimates (by one or more orders of magnitude) in epithelial Posm determinations, as shown by apparent streaming potentials during osmotic flow and by transiently reversed flows after removal of the proble. True Posm values for leaky epithelia probably exceed 10(-3) or 10(-2) cm/sec.osm. The necessary conditions for resolving osmotic transients are set out. 2. I illustrate the difficulties in deciding what fraction of transepithelial water flow is via the cells, and what fraction via the junctions. There is no existing method for answering this question. 3. Controversies about the validity, or need for modification, of the standing-gradient theory are discussed. Progress in this field requires new methods: to resolve osmotic transients; to separate transcellular and transjunctional water flows; and to measure solute concentrations in lateral intercellular spaces directly.

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Routes of nonelectrolyte permeability in gallbladder. Effects of 2,4,6-triaminopyrimidinium (TAP).

Cited by 28 publications

References 7 publications

Independence of net water flux from paracellular permeability in the intestine ofFundulus heteroclitus, a euryhaline teleost

Independence of net water flux from paracellular permeability in the intestine ofFundulus heteroclitus, a euryhaline teleost

Paracellular non‐electrolyte permeation during fluid transport across rabbit gall‐bladder epithelium

Osmotic water flow in leaky epithelia

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