FLUID MOVEMENTS ACROSS RABBIT ILEUM COUPLED TO PASSIVE PARACELLULAR ION MOVEMENTS

1. Theophylline (10 mM) and choleragen (1 x 10(‐6) g ml.‐1) abolish net fluid absorption by everted sacs of rabbit ileum. Triaminopyrimidine (20 mM) and ethacrynate (0.1 mM) prevent this inhibition of net fluid movement. Replacing Ringer Cl‐ with isethionate prevents the theophylline‐dependent decrease in fluid absorption also. 2. Ouabain (0.1 mM) abolishes net fluid movements in both control and theophylline‐treated tissue. 3. With ouabain present, hypertonic NaCl (200 mM) in the mucosal solution causes net fluid secretion (serosal‐mucosal flux). With theophylline added to both the mucosal and serosal solution, net fluid absorption (mucosal‐serosal flux) is observed (P less than 0.001). Triaminopyrimidine (20 mM), or ethacrynate (0.1 mM), or replacement of Ringer Na+ with choline, or Ringer Cl‐ with isethionate all prevent the theophylline‐induced reversal of osmotic flow. 4. Theophylline increases passive net flux of Na+ and Cl‐ from mucosal solution containing hypertonic (200 mM) NaCl+ ouabain (0.1 mM) across sheets of ileum into serosal solution containing mannitol Ringer + ouabain. The increased passive Na+ flux is blocked by triaminopyrimidine and the increased Na+ and Cl‐ fluxes are blocked by ethacrynate (0.1 mM). 5. The suggested route of increased NaCl leakage is via the paracellular pathway as it is inhibited by triaminopyrimidine. The increase, itself, is a consequence of the increased passive permeability of the mucosal border to Cl‐, induced by theophylline or choleragen. Water is apparently electro‐osmotically coupled to the paracellular Na+ leakage (100 mole water mole‐1 Na+), hence increased passive leakage reverses osmotic flow. In active tissue the lateral intercellular space contains hypertonic NaCl, and hence increased leakage of NaCl across the tight‐junction in theophylline or choleragen‐treated tissue gives rise to net fluid secretion. © 1979 The Physiological Society