Coordinated epithelial NHE3 inhibition and barrier dysfunction are required for TNF-mediated diarrhea in vivo
J. Clin. Invest. Daniel R. Clayburgh, et al. 116:2682 doi:10.1172/JCI29218 [Go to this article.]

Figure 4
NHE3 inhibition coupled with LIGHT injection leads to net water secretion. (A) LIGHT increases BSA flux into the perfused jejunal segment during in vivo perfusion assays regardless of treatment with S3226 or PMA. (B) LIGHT increases water absorption compared with that seen in control animals. Ten micromolar S3226 reduces water absorption in control animals (P = 0.02) and allows net water secretion in animals injected with LIGHT (P = 0.003). PMA also caused water malabsorption in control animals (P = 0.03) and net water secretion after LIGHT injection (P = 0.003). (C) Assay of NHE3^+/– (+/–) and NHE3^–/– (–/–) mice shows that both TNF and LIGHT cause increased BSA flux regardless of the presence of NHE3. (D) While NHE3^+/– mice display normal water absorption, NHE3^–/– mice have a significant quantitative defect (P = 0.02). TNF treatment of NHE3^+/– or NHE3^–/– mice caused net water loss similar to that in wild-type animals. LIGHT caused a nonsignificant increase in water absorption in NHE3^+/– mice but induced net water secretion in NHE3^–/– mice (P = 0.0003).