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 [
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Figure 3Induction of Na
+ malabsorption reverses water flux in LIGHT-treated animals.
(
A) Mice were injected with TNF, LIGHT, or vehicle and then perfused with solution containing Na
+ or the Na
+ substitute N-methyl-
d-glucamine where indicated. Both TNF and LIGHT treatment caused a significant increase in BSA flux compared with control, and perfusion with Na
+-free perfusate had no effect on the barrier dysfunction elicited by TNF or LIGHT. (
B) When perfused with solution lacking Na
+, control animals demonstrated a reduction in net water absorption (
P = 0.03). TNF injection caused net water secretion regardless of the presence of Na
+ in the perfusate. After LIGHT injection, perfusion with solution containing Na
+ resulted in an increase in water absorption compared with that in control animals (
P = 0.02), while perfusion with solution lacking Na
+ led to complete ablation of water absorption (
P = 0.008).