Morphologic and functional alterations in absorptive epithelial cells during L-tryptophan induced inhibition of net sodium and fluid absorption in the rat ileum.

ABSTRACT

L-Tryptophan (L-Trp) has been reported to suppress jejunal fluid and electrolyte transport in vitro, at a 20 mM concentration, whereas other amino acids enhance that absorption at the same concentration. The effect of L-Trp, glycine (Gly) and L-phenylalanine (L-Phe) on in vivo ileal and jejunal fluid and sodium transport, and their morphologic correlates, were investigated in the rat. In the ileum, morphology as well as fluid and sodium transport were more readily altered by L-Trp than in the jejunum. The ileal effects were rapid; morphologic and transport changes were seen within 2.5 minutes. The changes were stereospecific; they occurred only with the levo, but not with the dextro isomer of Trp. There was a concentration dependence; 20 mM levels of L-Trp were required, whereas lower concentrations of the amino acid often stimulated net absorption. Morphologic alterations produced by L-Trp were restricted to absorptive epithelial cells, whereas goblet cells appeared unaffected. Morphologically, L-Trp treatment led to the formation of clear basal vacuoles in ileal absorptive epithelial cells at 2.5 minutes, and extensive vacuolization and loss of the lumenal permeability barrier to macromolecules at 30 minutes. Since L-Trp can be hydroxylated in the small intestine, we assessed the effects of L-5 = OH tryptophan and 5-hydroxytryptamine on small intestinal transport and morphology in this experimental system. L-5-OH tryptophan inhibited fluid transport and produced some epithelial cell vacuolization. However, 5-hydroxytryptamine, which most severely decreased transport, had none of the morphologic effects of L-Trp. We hypothesize that L-Trp may inhibit transport as a result of its intracellular accumulation in absorptive epithelial cells.