Paracellular permeability of extracellular space markers across rat jejunum in vitro. Indication of a transepithelial fluid circuit.

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Abstract
The characteristics of [51Cr]EDTA, [3H]methoxyinulin ([3H]MI), [14C]polyethylene glycol-4000 ([14C]PEG) and [3H]mannitol as markers of the extracellular space (ECS) of isolated mucosa from the rat small intestine were examined. Unidirectional transmural fluxes across the rat jejunum of [3H]MI, [14C]PEG and [3H]mannitol were measured in the absence of glucose or the presence of 28 mM glucose. It is assumed that [14C]PEG does not enter the cells, [51Cr]EDTA and [3H]mannitol seem to have access to approximately 50 and 90% of the intracellular water, respectively. The commercially available [3H]MI had access to a space which exceeded the [14C]PEG space by 10%. Upon purification by gel filtration the high MW fraction of the [3H]MI provided estimates of the ECS identical with the estimates obtained with [14C]PEG. For all the markers used the ECS estimates remained constant between the 40th and 80th min of incubation. In the absence of glucose the transepithelial net fluxes of each of the different markers were zero. In the presence of 28 mM glucose the serosa-to-mucosa fluxes of all markers were dramatically increased. The ratio between the serosa-to-mucosa and the mucosa-to-serosa fluxes increased in the order [3H]mannitol > [3H]MI > [14C]PEG. The effect of glucose on the flux ratio of the marker substances suggests that glucose-induced net water transport to the serosa side of the gut wall represents the difference between a transcellular net water transport to the serosal side and a significant paracellular net water transport through the lateral intercellular spaces to the mucosal solution.