Measurements were made of the uptake of 14C-labelled sucrose in the short-circuited isolated midgut of fifth instar larvae of the tobacco hornworm. The longterm volume of distribution after bilateral exposure indicates that the extracellular space is about 0.26 ml g wet tissue, much less than has been previously suggested. The results of unilateral exposure yield a value of about 0.04 ml g−1 for luminal goblet cell cavities and 0.22 ml g−1 for interstitial space. The kinetics of uptake suggest that the interstitial space is best modelled as a distributed volume rather than as a single compartment. This mathematical result fits the physical picture of an interstitial fluid in long, narrow channels which communicate freely with the haemolymph but are nearly impermeable to sucrose at the luminal end; that is, they are sealed by septate junctions. The electrical conductance of the epithelium is high, but the transepithelial permeability to sucrose is very much lower than to K+. Thus, the tissue is a physically tight epithelium.

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