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

Net fluxes (Jsn) of sucrose, inulin, dextran (relative molecular mass 15000–17000), albumin and haemoglobin were measured across guineapig gall bladder unilateral preparations in which the absorptive flow (Jv) was varied over a wide range (without transepithelial osmotic gradients) by perfusing their lumina either with isosmotic solutions or with solutions of reduced osmolalities (a procedure that increased Jv). The absorptive flow Jv was inhibited by 10–4M ouabain. The net flux Jsn was a linear function of Jv for sucrose, inulin and dextran, the slopes being inversely related to the size of the solute. Albumin and haemoglobin barely crossed the preparation. The large increase in Jsn cannot be accounted for by increased leakiness of the preparation or by unstirred layer effects. The logarithms of the unidirectional flux ratios for sucrose, inulin and dextran in bilateral preparation were also linear functions of Jv. 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 Jsn for sucrose was also a linear function of Jv in experiments performed only at the physiological osmolality (0.3osm). This value is calculated from the slope of the line relating Jsn to Jv.