PAF regulates mucosal barrier function of rat small intestine: Possible role of tyrosine phosphorylation of E-cadherin

Infusion of low doses of PAF into the splanchnic circulation increased intestinal mucosal permeability. Further, PAF antagonists prevented mucosal permeability increase induced by nitric oxide synthase inhibitors. Thus, PAF may modulate intestinal mucosal permeablility. Here we examined the mechanism of the PAF effect on mucosal barrier. Adult S.D. rats were injected with low dose of PAF (1.25 μg/kg, i.V.), which did not cause intestinal injury. Mucosal permeability was assessed by the lumen-to-plasma entry of FITC-dextran 4,000. Tyrosine phosphorylation of E-cadherin (a component of adherens junction) was detected with western blot following immune-precipitation. We found that 5 min after PAF, a punctate pattern of F-actin staining was noted focally at villus tips. 30 min after PAF, the linear outline of the brush border as well as paracellular junction at the villus tip was lost. Intestinal permeability increased 17-fold 60 min after PAF. Further, tyrosine phosphorylation of intestinal E-cadherin was enhanced 30 min after PAF. Thus, PAF may induce disruption of the intestinal epithelial cytoskeleton and tyrosine phosphorylation of adherens junction complex, increasing paracellular permeability and access of luminal contents to the systemic circulation.