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

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Abstract
Mucosa-to-serosa fluxes of 7 polar nonelectrolytes were determined during isotonic fluid transport across the unilateral rabbit gallbladder preparation in an attempt to estimate the contribution of the paracellular pathway to the total transepithelial water flow. 3H- and 14C-labeled nonelectrolyte tracers appeared in the transported fluid at fractions (fn) 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 and inulin, 0.02. The mean volume flow rate was 78 .mu.l .cntdot. cm-2 h-1. While the fluxes of the larger molecules were probably due to diffusion through a small but unrestricted paracellular shunt permeability, the high fn values obtained for the smaller molecules indicate the existence of a substantial paracellular permeability restricted to molecules smaller than erythritol. Upper limits to the transcellular ethanediol and thiourea permeabilities, estimated from the time constants of tracer 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. Comparison of the fn 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 > 1/2 of the transepithelial water flow must follow the paracellular pathway. Following a reduction of the mucosal osmolality to 110 m-osmol kg-1, the apparent nonelectrolyte permeability of the epithelium increased steadily over a period of 4 h. This seems to reflect an increase in the shunt permeability rather than a change in the selectivity of the restricted permeability. During isotonic fluid transport, the bulk of the transepithelial water flow crossing the epithelium apparently passes through paracellular channels of .apprx. 3 .ANG. radius which are probably located in the intercellular junction.

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