Solvent drag of large solutes indicates paracellular water flow in leaky epithelia

Net fluxes J(s,n) of sucrose, insulin, dextran (relative molecular mass 15000-17000), albumin and haemoglobin were measured across guinea-pig gall bladder unilateral preparations in which the absorptive flow J(v) was varied over a wide range (without transepithelial osmotic gradients) by perfusing their lamina either with isosmotic solutions or with solutions of reduced osmolalities (a procedure that increased J(v)). The absorptive flow J(v) was inhibited by 10^-4M ouabain. The net flux J(s,n) was a linear function of J(v) for sucrose, insulin and dextran, the slopes being inversely related to the size of the solute. Albumin and haemoglobin barely crossed the preparation. The large increase in J(s,n) cannot be accounted for by increased leakiness of the preparation or by unstirred layer effects. The logarithms of the unidirectional flux ratios for sucrose, insulin and dextran in bilateral preparation were also linear functions of J(v). It is concluded that solvent drags these solutes via the paracellular pathway. More than 50% of the water flows paracellularly also under normal physiological conditions, since J(s,n) for sucrose was also a linear function of J(v) in experiments performed only at the physiological osmolality (0.3 osm). This value is calculated from the slope of the line relating J(s,n) to J(v).