Effect of protonated 2,4,6-triaminopyrimidine, a tight junction blocker, on intestinal transport in dog ileum in vivo

Abstract

Previous in vitro experiments suggest that protonated 2,4,6-triaminopyrimidine (TAP+) inhibits passive Na+ movement across tight junctions of various epithelial tissues. So far no evidence has been found that TAP+ interferes with other mucosal transport processes. Because blockage of the tight junctions would be a promising tool in studying intestinal transport physiology, the effect of TAP+ was investigated in the dog ileum in vivo. When TAP+ was added to a sodium-free mannitol solution, the transepithelial sodium diffusion potential was significantly decreased (60% inhibition with 34 mm TAP+); this would be expected if TAP+ inhibited NA+ permeation through tight junctions. However, TAP+ was also found to diminish Na+ and Cl- absorption. Furthermore, TAP+ increased unidirectional Na+ flux from plasma to lumen; this is opposite to the expected result of tight junction blockage. In addition, TAP+ reduced glucose, fructose, and xylose absorption by about 50%. In ileal loops exposed to cholera toxin, TAP+ enhanced secretion by a rate equal to the rate by which it reduced absorption in loops not exposed to cholera toxin. All changes induced by TAP+ approached normal within 4 hr of its removal from the perfusate. TAP+ did not cause nay mucosal damage that could be detected by protein leakage or by light microscopy. These studies show that TAP+ has many effects on intestinal transport processes that cannot be explained on the basis of tight junction blockage.