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

Abstract

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.

Interaction between transcellular and paracellular water transport pathways through Aquaporin 5 and the tight junction complex

“…To date, such tracers are not available, prompting investigators to use labeled dextran particles (which are not transported by the transcellular pathway) to estimate the amount of water transported through the paracellular pathway (5,(13)(14)(15). Although complex biophysical differences between FITC-D and water molecules limit the use of this tracer in determining the absolute amount of water transported, labeled dextran particles have been used effectively to determine ratios of paracellular permeability (24,25). We therefore chose FITC-D to compare paracellular permeability in salivary glands of AQP5ϩ/ϩ and AQP5Ϫ/Ϫ mice based on the successful use of such tracers in rat salivary glands (5,26,27).…”

Current‐induced volume flow across bovine tracheal epithelium: evidence for sodium‐water coupling.

“…J, associated with active salt transport, is a transcellular event, a concept which led to the standing-gradient osmotic flow theory (Diamond & Bossert, 1967), was critically re-examined (Sackin & Boulpaep, 1975;Hill, 1975 a). Convincing evidence has accumulated, indicating that the paracellular pathway is an important and perhaps the main route of ion and water permeation through leaky epithelia (Fr6mter, 1972;Frbmter & Diamond, 1972;Frizzell & Shultz, 1972;Whittembury et al 1980;Steward, 1982). It is generally accepted that the intercellular junctions are not merely electrical and hydraulic shunt pathways, but that they possess conspicuous selectivity properties for ions and non-electrolytes.…”

“…The classical view that volume flow (Jv) is an exclusively transcellular process has been modified and there is now strong evidence showing that an appreciable part of water flows through the intercellular junctions in leaky epithelia (Whittembury, Verde de Martinez, Linares & Paz-Aliaga, 1980;Steward, 1982).…”

Active sodium transport and fluid secretion in the gall‐bladder epithelium of Necturus.

“…Ifthis is so it would mean that all the salt is transported through a transcellular route. This implies that if, as indicated by recent experiments, the movements of water occur mainly through the intercellular junctions (Hill & Hill, 1978b;Whitembury et al 1980;Steward, 1982), the net result ought to be a solute-free junctional water flow. To reconcile these two basic observations on the path followed by salt and water during isotonic transport and to explain the properties of the intercellular junctions so as to allow such behaviour seem to be major problems for any theory of fluid absorption in epithelia.…”

“…Both processes are known to be linked, but the precise mechanism of coupling is far from being understood. There are in principle two parallel pathways available for the transport of salt and water in leaky epithelia, namely cellular and paracellular, and recent evidence suggests that the movement ofwater occurs mainly through a paracellular route (Hill & Hill, 1978 b; Whittembury, Verde de Martinez, Linares & Paz-Aliaga, 1980;Steward, 1982). Since it is well established that the intercellular junctions are highly permeable to monovalent cations (Fromter, 1972;Reuss & Finn, 1975;Van Os & Slegers, 1975) the question then arises as to whether the main route for the transport of Na during fluid absorption is transcellular or paracellular.…”